118 results on '"Xiang-Hang Luo"'
Search Results
2. Correction: Mutated lncRNA increase the risk of type 2 diabetes by promoting β cell dysfunction and insulin resistance
- Author
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Wan-Hui Guo, Qi Guo, Ya-Lin Liu, Dan-Dan Yan, Li Jin, Rong Zhang, Jing Yan, Xiang-Hang Luo, and Mi Yang
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Cancer Research ,Cellular and Molecular Neuroscience ,Immunology ,Cell Biology - Published
- 2022
3. Mutated lncRNA increase the risk of type 2 diabetes by promoting β cell dysfunction and insulin resistance
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Wan-Hui Guo, Qi Guo, Ya-Lin Liu, Dan-Dan Yan, Li Jin, Rong Zhang, Jing Yan, Xiang-Hang Luo, and Mi Yang
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Mice ,Islets of Langerhans ,Cancer Research ,Cellular and Molecular Neuroscience ,Diabetes Mellitus, Type 2 ,Insulin-Secreting Cells ,Immunology ,Animals ,Insulin ,Humans ,RNA, Long Noncoding ,Cell Biology ,Insulin Resistance - Abstract
Islet β cell dysfunction and insulin resistance are the main pathogenesis of type 2 diabetes (T2D), but the mechanism remains unclear. Here we identify a rs3819316 C > T mutation in lncRNA Reg1cp mainly expressed in islets associated with an increased risk of T2D. Analyses in 16,113 Chinese adults reveal that Mut-Reg1cp individuals had higher incidence of T2D and presented impaired insulin secretion as well as increased insulin resistance. Mice with islet β cell specific Mut-Reg1cp knock-in have more severe β cell dysfunction and insulin resistance. Mass spectrometry assay of proteins after RNA pulldown demonstrate that Mut-Reg1cp directly binds to polypyrimidine tract binding protein 1 (PTBP1), further immunofluorescence staining, western blot analysis, qPCR analysis and glucose stimulated insulin secretion test reveal that Mut-Reg1cp disrupts the stabilization of insulin mRNA by inhibiting the phosphorylation of PTBP1 in β cells. Furthermore, islet derived exosomes transfer Mut-Reg1cp into peripheral tissue, which then promote insulin resistance by inhibiting AdipoR1 translation and adiponectin signaling. Our findings identify a novel mutation in lncRNA involved in the pathogenesis of T2D, and reveal a new mechanism for the development of T2D.
- Published
- 2022
4. Endocrine role of bone in the regulation of energy metabolism
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Changjun Li, Qi Guo, Yan Huang, Xiang-Hang Luo, Ruoyu Zhou, Qiaoyue Guo, and Ye Xiao
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Calcium metabolism ,Histology ,business.industry ,Mechanism (biology) ,QH301-705.5 ,Physiology ,Endocrinology, Diabetes and Metabolism ,Osteoporosis ,Regulator ,Review Article ,Multihormonal system disorders ,Bioinformatics ,medicine.disease ,Metabolic syndrome ,Bone remodeling ,medicine ,Endocrine system ,QP1-981 ,Biology (General) ,business ,Homeostasis - Abstract
sBone mainly functions as a supportive framework for the whole body and is the major regulator of calcium homeostasis and hematopoietic function. Recently, an increasing number of studies have characterized the significance of bone as an endocrine organ, suggesting that bone-derived factors regulate local bone metabolism and metabolic functions. In addition, these factors can regulate global energy homeostasis by altering insulin sensitivity, feeding behavior, and adipocyte commitment. These findings may provide a new pathological mechanism for related metabolic diseases or be used in the diagnosis, treatment, and prevention of metabolic diseases such as osteoporosis, obesity, and diabetes mellitus. In this review, we summarize the regulatory effect of bone and bone-derived factors on energy metabolism and discuss directions for future research.
- Published
- 2021
5. Orchestration of alternative splicing regulates bone marrow mesenchymal stem cells fate during aging
- Author
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Ye Xiao, Guang-Ping Cai, Xu Feng, Qi Guo, Yan Huang, Tian Su, Chang-Jun Li, Xiang-Hang Luo, Yong-Jun Zheng, and Mi Yang
- Abstract
Senescence and change of differentiation direction in bone marrow stromal cells (BMSCs) are two of the most important causes of age-related bone loss. As an important post-transcriptional regulatory pathway, alternative splicing (AS) regulates diversity of gene expression. However, the role of AS in BMSCs during aging remains poorly defined. Here we identify AS in specific genes disrupt gene expression pattern and result in age-related debility of BMSCs. We demonstrate the deficiency of splicing factor Y-box protein 1 (YBX1) result in mis-splicing in genes such as Fn1, Taz, Sirt2 and Sp7, further contributing to senescence and shift in differentiation direction of BMSCs during aging. Deletion or over-expression of YBX1 in BMSCs accelerate bone loss or stimulate bone formation in mice. Notably, we identify a small compound sciadopitysin which attenuate the degradation of YBX1 and attenuate bone loss in old mice. Our study demonstrates elaborately controlled RNA splicing governs cell fate of BMSCs and provides a potential therapeutic target for age-related osteoporosis.SummaryThis study demonstrates that YBX1 deficiency induces pre-mRNA mis-splicing and causes senescence and shift in differentiation direction of BMSCs and further accelerates aging-related bone loss. This study identifies Sciadopitysin could reverse this process by targeting YBX1.
- Published
- 2022
6. The role of autophagy in bone homeostasis
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Changjun Li, Qi Guo, Tian Su, Mi Yang, Yi‐Fan Guo, Ya Liu, Xiang-Hang Luo, Yan Huang, and Ye Xiao
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0301 basic medicine ,Physiology ,Clinical Biochemistry ,Osteoporosis ,Autophagy-Related Proteins ,Cellular homeostasis ,Biology ,Bone and Bones ,03 medical and health sciences ,0302 clinical medicine ,Osteoclast ,Osteoarthritis ,Bone cell ,Autophagy ,medicine ,Animals ,Homeostasis ,Humans ,Bone Density Conservation Agents ,Mechanism (biology) ,Osteoblast ,Cell Biology ,Osteitis Deformans ,medicine.disease ,Cell biology ,030104 developmental biology ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Bone Remodeling - Abstract
Autophagy is an evolutionarily conserved intracellular process and is considered one of the main catabolism pathways. In the process of autophagy, cells are digested nonselectively or selectively to recover nutrients and energy, so it is regarded as an antiaging process. In addition to the essential role of autophagy in cellular homeostasis, autophagy is a stress response mechanism for cell survival. Here, we review recent literature describing the pathway of autophagy and its role in different bone cell types, including osteoblasts, osteoclasts, and osteocytes. Also discussed is the mechanism of autophagy in bone diseases associated with bone homeostasis, including osteoporosis and Paget's disease. Finally, we discuss the application of autophagy regulators in bone diseases. This review aims to introduce autophagy, summarize the understanding of its relevance in bone physiology, and discuss its role and therapeutic potential in the pathogenesis of bone diseases such as osteoporosis.
- Published
- 2021
7. Identification of SCARA3 with potential roles in metabolic disorders
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Qi Guo, Xiang-Hang Luo, Tian Su, Changjun Li, Hui Peng, Yan Huang, and Ye Xiao
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Male ,obesity ,Aging ,medicine.medical_specialty ,Adipose Tissue, White ,Adipose tissue ,White adipose tissue ,Type 2 diabetes ,Biology ,Diet, High-Fat ,Pathogenesis ,Mice ,SCARA3 ,Internal medicine ,Databases, Genetic ,medicine ,metabolic disorders ,Animals ,Humans ,Gene Regulatory Networks ,Scavenger receptor ,Heat-Shock Proteins ,Adipogenesis ,Mesenchymal stem cell ,Scavenger Receptors, Class A ,Cell Biology ,DNA Methylation ,Atherosclerosis ,medicine.disease ,Endocrinology ,Diabetes Mellitus, Type 2 ,DNA methylation ,Receptors, Leptin ,methylation ,Research Paper - Abstract
Obesity is characterized by the expansion of adipose tissue which is partially modulated by adipogenesis. In the present study, we identified five differentially expressed genes by incorporating two adipogenesis-related datasets from the GEO database and their correlation with adipogenic markers. However, the role of scavenger receptor class A member 3 (SCARA3) in obesity-related disorders has been rarely reported. We found that Scara3 expression in old adipose tissue-derived mesenchymal stem cells (Ad-MSCs) was lower than it in young Ad-MSCs. Obese mice caused by deletion of the leptin receptor gene (db/db) or by a high-fat diet both showed reduced Scara3 expression in inguinal white adipose tissue. Moreover, hypermethylation of SCARA3 was observed in patients with type 2 diabetes and atherosclerosis. Data from the CTD database indicated that SCARA3 is a potential target for metabolic diseases. Mechanistically, JUN was predicted as a transcriptional factor of SCARA3 in different databases which is consistent with our further bioinformatics analysis. Collectively, our study suggested that SCARA3 is potentially associated with age-related metabolic dysfunction, which provided new insights into the pathogenesis and treatment of obesity as well as other obesity-associated metabolic complications.
- Published
- 2020
8. miR-188-3p targets skeletal endothelium coupling of angiogenesis and osteogenesis during ageing
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Wen-Zhen He, Mi Yang, Yangzi Jiang, Chen He, Yu-Chen Sun, Ling Liu, Mei Huang, Yu-Rui Jiao, Kai-Xuan Chen, Jing Hou, Min Huang, Yi-Li Xu, Xu Feng, Ya Liu, Qi Guo, Hui Peng, Yan Huang, Tian Su, Ye Xiao, Yusheng Li, Chao Zeng, Guanghua Lei, Xiang-Hang Luo, and Chang-Jun Li
- Subjects
Cancer Research ,Cellular and Molecular Neuroscience ,Aging ,Mice ,MicroRNAs ,Neovascularization, Pathologic ,Osteogenesis ,Immunology ,Animals ,Endothelial Cells ,Cell Biology ,Endothelium - Abstract
A specific bone capillary subtype, namely type H vessels, with high expression of CD31 and endomucin, was shown to couple angiogenesis and osteogenesis recently. The number of type H vessels in bone tissue declines with age, and the underlying mechanism for this reduction is unclear. Here, we report that microRNA-188-3p (miR-188-3p) involves this process. miRNA-188-3p expression is upregulated in skeletal endothelium and negatively regulates the formation of type H vessels during ageing. Mice with depletion of miR-188 showed an alleviated age-related decline in type H vessels. In contrast, endothelial-specific overexpression of miR-188-3p reduced the number of type H vessels, leading to decreased bone mass and delayed bone regeneration. Mechanistically, we found that miR-188 inhibits type H vessel formation by directly targeting integrin β3 in endothelial cells. Our findings indicate that miR-188-3p is a key regulator of type H vessel formation and may be a potential therapeutic target for preventing bone loss and accelerating bone regeneration.
- Published
- 2021
9. A mechanosensitive lipolytic factor in the bone marrow promotes osteogenesis and lymphopoiesis
- Author
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Hui Peng, Biao Hu, Ling-Qi Xie, Tian Su, Chang-Jun Li, Ya Liu, Mi Yang, Ye Xiao, Xu Feng, Rui Zhou, Qi Guo, Hai-Yan Zhou, Yan Huang, Tie-Jian Jiang, and Xiang-Hang Luo
- Subjects
Mice ,Bone Marrow ,Osteogenesis ,Physiology ,Lipolysis ,Lymphopoiesis ,Animals ,Bone Marrow Cells ,Cell Differentiation ,Mesenchymal Stem Cells ,Cell Biology ,Molecular Biology ,Cells, Cultured - Abstract
Exercise can prevent osteoporosis and improve immune function, but the mechanism remains unclear. Here, we show that exercise promotes reticulocalbin-2 secretion from the bone marrow macrophages to initiate bone marrow fat lipolysis. Given the crucial role of lipolysis in exercise-stimulated osteogenesis and lymphopoiesis, these findings suggest that reticulocalbin-2 is a pivotal regulator of a local adipose-osteogenic/immune axis. Mechanistically, reticulocalbin-2 binds to a functional receptor complex, which is composed of neuronilin-2 and integrin beta-1, to activate a cAMP-PKA signaling pathway that mobilizes bone marrow fat via lipolysis to fuel the differentiation and function of mesenchymal and hematopoietic stem cells. Notably, the administration of recombinant reticulocalbin-2 in tail-suspended and old mice remarkably decreases bone marrow fat accumulation and promotes osteogenesis and lymphopoiesis. These findings identify reticulocalbin-2 as a novel mechanosensitive lipolytic factor in maintaining energy homeostasis in bone resident cells, and it provides a promising target for skeletal and immune health.
- Published
- 2022
10. Krüppel-like factor 3 inhibition by mutated lncRNA Reg1cp results in human high bone mass syndrome
- Author
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Ye Xiao, Hui-Ling Chen, Changjun Li, Hui Peng, Qi Guo, Mi Yang, Tian Su, Min-Xiang Lei, T. Jiang, Xiang-Hang Luo, Yun-Lin Zhang, Yan Huang, and Yuzhong Xiao
- Subjects
0301 basic medicine ,Mutation ,Endothelium ,Bone density ,Chemistry ,Angiogenesis ,Immunology ,Mutant ,Osteoporosis ,Gene mutation ,medicine.disease ,medicine.disease_cause ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Cancer research ,medicine ,Immunology and Allergy ,Bone marrow - Abstract
High bone mass (HBM) is usually caused by gene mutations, and its mechanism remains unclear. In the present study, we identified a novel mutation in the long noncoding RNA Reg1cp that is associated with HBM. Subsequent analysis in 1,465 Chinese subjects revealed that heterozygous Reg1cp individuals had higher bone density compared with subjects with WT Reg1cp. Mutant Reg1cp increased the formation of the CD31hiEmcnhi endothelium in the bone marrow, which stimulated angiogenesis during osteogenesis. Mechanistically, mutant Reg1cp directly binds to Krüppel-like factor 3 (KLF3) to inhibit its activity. Mice depleted of Klf3 in endothelial cells showed a high abundance of CD31hiEmcnhi vessels and increased bone mass. Notably, we identified a natural compound, Ophiopogonin D, which functions as a KLF3 inhibitor. Administration of Ophiopogonin D increased the abundance of CD31hiEmcnhi vessels and bone formation. Our findings revealed a specific mutation in lncRNA Reg1cp that is involved in the pathogenesis of HBM and provides a new target to treat osteoporosis.
- Published
- 2019
11. Current Progress on MicroRNA-Based Gene Delivery in the Treatment of Osteoporosis and Osteoporotic Fracture
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Stephen P. Robertson, Xi Sun, Xiang-Hang Luo, Wenhua Wei, Ying Yuan, and Qi Guo
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0301 basic medicine ,lcsh:RC648-665 ,Endocrine and Autonomic Systems ,business.industry ,Endocrinology, Diabetes and Metabolism ,Regeneration (biology) ,Osteoporosis ,Review Article ,Gene delivery ,Bioinformatics ,medicine.disease ,lcsh:Diseases of the endocrine glands. Clinical endocrinology ,Bone remodeling ,Clinical Practice ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Endocrinology ,030220 oncology & carcinogenesis ,microRNA ,Medicine ,Osteoporotic fracture ,business - Abstract
Emerging evidence demonstrates that microRNAs, as important endogenous posttranscriptional regulators, are essential for bone remodeling and regeneration. Undoubtedly, microRNA-based gene therapies show great potential to become novel approaches against bone-related diseases, including osteoporosis and associated fractures. The major obstacles for continued advancement of microRNA-based therapies in clinical application include their poorin vivostability, nonspecific biodistribution, and unwanted side effects. Appropriate chemical modifications and delivery vectors, which improve the biological performance and potency of microRNA-based drugs, hold the key to translating miRNA technologies into clinical practice. Thus, this review summarizes the current attempts and existing deficiencies of chemical modifications and delivery systems applied in microRNA-based therapies for osteoporosis and osteoporotic fractures to inform further explorations.
- Published
- 2019
12. Long noncoding RNA Gm31629 protects against mucosal damage in experimental colitis via YB-1/E2F pathway
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Xu Feng, Ye Xiao, Jian He, Mi Yang, Qi Guo, Tian Su, Yan Huang, Jun Yi, Chang-Jun Li, Xiang-Hang Luo, Xiao-Wei Liu, and Hai-Yan Zhou
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Inflammation ,Mice, Inbred C57BL ,Disease Models, Animal ,Mice ,Dextran Sulfate ,Animals ,RNA, Long Noncoding ,General Medicine ,Intestinal Mucosa ,Colitis ,Inflammatory Bowel Diseases ,Transcription Factors - Abstract
Mucosal healing is a key treatment goal for inflammatory bowel disease, and adequate epithelial regeneration is required for an intact gut epithelium. However, the underlying mechanism for mucosal healing is unclear. Long noncoding RNAs (lncRNAs) have been reported to be involved in the development of inflammatory bowel disease. Here, we report that a lncRNA named Gm31629 decreased in intestinal epithelial cells in response to inflammatory stimulation. Gm31629 deficiency led to exacerbated intestinal inflammation and delayed epithelial regeneration in dextran sulfate sodium-induced (DSS-induced) colitis model. Mechanistically, Gm31629 promoted E2F pathways and cell proliferation by stabilizing Y-box protein 1 (YB-1), thus facilitating epithelial regeneration. Genetic overexpression of Gm31629 protected against DSS-induced colitis in vivo. Theaflavin 3-gallate, a natural compound mimicking Gm31629, alleviated DSS-induced epithelial inflammation and mucosal damage. These results demonstrate an essential role of lncRNA Gm31629 in linking intestinal inflammation and epithelial cell proliferation, providing a potential therapeutic approach to inflammatory bowel disease.
- Published
- 2021
13. Grancalcin in Immune Cells is Induced and Regulates Bone-Fat Imbalance During Skeletal Aging
- Author
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Changjun Li, Yan Huang, Yu-Chen Sun, Mi Yang, Ye Xiao, Qi Guo, Xiang-Hang Luo, and Tian Su
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biology ,Osteoporosis ,Grancalcin ,medicine.disease ,Phenotype ,Cell biology ,Bone remodeling ,medicine.anatomical_structure ,Immune system ,medicine ,biology.protein ,Bone marrow ,skin and connective tissue diseases ,Neutralizing antibody ,Receptor - Abstract
Skeletal aging is characterized by low bone turnover and increased marrow fat accumulation. However, the underlying mechanism remains poorly defined. Here we show that pro-inflammatory and senescent subtypes of immune cells, including macrophages and neutrophils, accumulated in bone marrow and secreted abundant grancalcin (GCA) during aging. Elevation of bone marrow GCA level in young mice leads to premature skeletal aging. Deletion of GCA in neutrophils and macrophages rejuvenates skeletal aging. Mechanistically, we identify that GCA binds to Plexin-b2 receptor and inactivates its downstream pathway. Depletion of plexin-b2 in bone marrow mesenchymal stem cells abrogates the rejuvenated bone phenotype of GCA-knockout mice. Moreover, GCA neutralizing antibody is generated and shows a certain rejuvenating effect on bone. Given that immune cells are involved into diverse pathologic processes, targeting this fundamental mechanism to prevent skeletal aging offers novel treatment strategy not only for osteoporosis, but also for multiple age-related diseases.
- Published
- 2021
14. Regulation of bone marrow mesenchymal stem cell fate by long non-coding RNA
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Qi Guo, Changjun Li, Xiang-Hang Luo, Qiaoyue Guo, Yan Huang, and Ye Xiao
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0301 basic medicine ,Histology ,Physiology ,Endocrinology, Diabetes and Metabolism ,030209 endocrinology & metabolism ,Bone Marrow Cells ,Biology ,03 medical and health sciences ,0302 clinical medicine ,stomatognathic system ,Osteogenesis ,medicine ,Progenitor cell ,Transcription factor ,Adipogenesis ,Osteoblasts ,Mesenchymal stem cell ,Wnt signaling pathway ,Cell Differentiation ,Mesenchymal Stem Cells ,Long non-coding RNA ,Cell biology ,030104 developmental biology ,medicine.anatomical_structure ,RNA, Long Noncoding ,Bone marrow ,Signal transduction - Abstract
Bone mesenchymal stem cells (BMSCs) are progenitor cells isolated from bone marrow, which keep potential to differentiate into several kinds of cells including osteoblasts and adipocytes. A dynamic mutual regulation exists between osteogenesis and adipogenesis processes. Long non-coding RNA (lncRNA) performs diverse functions in biological activities including regulation of BMSCs commitment. Evidence has shown that lncRNA regulates key signaling pathways including TGFβ/BMP, Wnt and Notch pathways, and several transcription factors in BMSCs differention. Dysregulation of lncRNA in BMSCs leads to disruption of osteo-adipogenesis difffrentiation and results in impairment of bone homeostasis. In this review, we focus on the role of lncRNA in several critical signaling pathways that involved in regulation of osteo-adipogenesis of BMSC and prospects the potential clinical application of lncRNA.
- Published
- 2020
15. The Role of Bone-Derived Exosomes in Regulating Skeletal Metabolism and Extraosseous Diseases
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Huili Lyu, Qi Guo, Yan Huang, Ye Xiao, and Xiang Hang Luo
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0301 basic medicine ,Stromal cell ,Potential candidate ,Review ,Exosome ,Cell and Developmental Biology ,03 medical and health sciences ,0302 clinical medicine ,medicine ,exosome ,bone tissue engineering ,lcsh:QH301-705.5 ,Chemistry ,skeletal metabolism ,Cell Biology ,Metabolism ,Microvesicles ,Cell biology ,030104 developmental biology ,medicine.anatomical_structure ,lcsh:Biology (General) ,030220 oncology & carcinogenesis ,Drug delivery ,biomarker ,Bone marrow ,extraosseous diseases ,Intracellular ,Developmental Biology - Abstract
Bone-derived exosomes are naturally existing nano-sized extracellular vesicles secreted by various cells, such as bone marrow stromal cells, osteoclasts, osteoblasts, and osteocytes, containing multifarious proteins, lipids, and nucleic acids. Accumulating evidence indicates that bone-derived exosomes are involved in the regulation of skeletal metabolism and extraosseous diseases through modulating intercellular communication and the transfer of materials. Following the development of research, we found that exosomes can be considered as a potential candidate as a drug delivery carrier thanks to its ability to transport molecules into targeted cells with high stability, safety, and efficiency. This review aims to discuss the emerging role of bone-derived exosomes in skeletal metabolism and extraosseous diseases as well as their potential role as candidate biomarkers or for developing new therapeutic strategies.
- Published
- 2020
16. Ophiopogonin D promotes bone regeneration by stimulating CD31hiEMCNhi vessel formation
- Author
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Mi Yang, Tian Su, Changjun Li, Xiang-Hang Luo, Qi Guo, Yan Huang, Ye Xiao, and T. Jiang
- Subjects
0301 basic medicine ,CD31 ,Male ,Bone Regeneration ,Angiogenesis ,Sialoglycoproteins ,Kruppel-Like Transcription Factors ,Krüppel like factor 3 ,Neovascularization, Physiologic ,Bone healing ,03 medical and health sciences ,Mice ,0302 clinical medicine ,In vivo ,Osteogenesis ,medicine ,Spirostans ,Animals ,Platelet ,Bone regeneration ,Cells, Cultured ,Mice, Knockout ,Chemistry ,Ophiopogonin D ,Cell Biology ,General Medicine ,Bone fracture ,Original Articles ,Saponins ,medicine.disease ,Cell biology ,Mice, Inbred C57BL ,Platelet Endothelial Cell Adhesion Molecule-1 ,030104 developmental biology ,030220 oncology & carcinogenesis ,Knockout mouse ,cardiovascular system ,Original Article ,CD31hiEMCNhi vessel - Abstract
OBJECTIVES CD31hi EMCNhi vessels (CD31, also known as PECAM1 [platelet and endothelial cell adhesion molecule 1]; EMCN, endomucin), which are strongly positive for CD31 and endomucin, couple angiogenesis and osteogenesis. However, the role of CD31hi EMCNhi vessels in bone regeneration remains unknown. In the present study, we investigated the role of CD31hi EMCNhi vessels in the process of bone regeneration. MATERIALS AND METHODS We used endothelial-specific Kruppel like factor 3 (Klf3) knockout mice and ophiopogonin D treatment to interfere with CD31hi EMCNhi vessel formation. We constructed a bone regeneration model by surgical ablation of the trabecular bone. Immunofluorescence and micro-computed tomography (CT) were used to detect CD31hi EMCNhi vessels and bone formation. RESULTS CD31hi EMCNhi vessels participate in the process of bone regeneration, such that endothelial-specific Klf3 knockout mice showed increased CD31hi EMCNhi vessels and osteoprogenitors in the bone regeneration area, and further accelerated bone formation. We also demonstrated that the natural compound, ophiopogonin D, acts as a KLF3 inhibitor to promote vessels formation both in vitro and in vivo. Administration of ophiopogonin D increased the abundance of CD31hi Emcnhi vessels and accelerated bone healing. CONCLUSIONS Our findings confirmed the important role of CD31hi Emcnhi vessels in bone regeneration and provided a new target to treat bone fracture or promote bone regeneration.
- Published
- 2020
17. MicroRNAs and Osteoblasts Differentiation
- Author
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Xu Feng, Qiaoyue Guo, Xiang-Hang Luo, Qi Guo, and Xi Sun
- Subjects
Cellular differentiation ,microRNA ,Gene expression ,Wnt signaling pathway ,Signal transduction ,Cell cycle ,Biology ,Homeostasis ,Cell biology ,Bone remodeling - Abstract
Numerous studies of single stranded endogenous ~ 22 nt microRNAs (miRNAs) have demonstrated their diverse biological functions including control of cell differentiation, cell cycle and pathological conditions. Recent studies suggest the application of miRNAs as ideal biomarkers and therapeutic targets. miRNAs play a vital role as post-transcriptional regulators of gene expression which controls osteoblasts mediated bone formation and osteoclasts related bone remodeling. Also, miRNAs regulate the differentiation of osteoblasts and osteogenesis. The differentiation of osteoblasts is crucial to the regulation of bone homeostasis and it is involved in triggering several signaling pathways like TGF-β, BMP and Wnt, which are regulated by miRNAs. This chapter summarizes the role of miRNAs in osteoblasts differentiation and emphasizes their potential therapeutic role in metabolic bone disorders.
- Published
- 2020
18. MicroRNA‐188 regulates aging‐associated metabolic phenotype
- Author
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Tian Su, Fangliang Zhou, Ya Liu, Ting Liu, Qi Guo, Ye Xiao, Yan Huang, Min Guo, Xiang-Hang Luo, and Yuzhong Xiao
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Male ,0301 basic medicine ,Genetically modified mouse ,Aging ,medicine.medical_specialty ,aging‐associated metabolic phenotype ,inguinal white adipose tissue ,PRDM16 ,Adipose tissue ,White adipose tissue ,Biology ,Transfection ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,energy expenditure ,microRNA ,Brown adipose tissue ,medicine ,Animals ,Humans ,MicroRNA‐188 ,Mice, Knockout ,Original Paper ,brown adipose tissue ,Cell Biology ,Original Papers ,Phenotype ,MicroRNAs ,030104 developmental biology ,Endocrinology ,medicine.anatomical_structure ,Knockout mouse ,030217 neurology & neurosurgery - Abstract
With the increasing aging population, aging‐associated diseases are becoming epidemic worldwide, including aging‐associated metabolic dysfunction. However, the underlying mechanisms are poorly understood. In the present study, we aimed to investigate the role of microRNA miR‐188 in the aging‐associated metabolic phenotype. The results showed that the expression of miR‐188 increased gradually in brown adipose tissue (BAT) and inguinal white adipose tissue (iWAT) of mice during aging. MiR‐188 knockout mice were resistant to the aging‐associated metabolic phenotype and had higher energy expenditure. Meanwhile, adipose tissue‐specific miR‐188 transgenic mice displayed the opposite phenotype. Mechanistically, we identified the thermogenic‐related gene Prdm16 (encoding PR domain containing 16) as the direct target of miR‐188. Notably, inhibition of miR‐188 expression in BAT and iWAT of aged mice by tail vein injection of antagomiR‐188 ameliorated aging‐associated metabolic dysfunction significantly. Taken together, our findings suggested that miR‐188 plays an important role in the regulation of the aging‐associated metabolic phenotype, and targeting miR‐188 could be an effective strategy to prevent aging‐associated metabolic dysfunction., 1) MiR‐188 expression increased gradually in the BAT and iWAT of mice during aging. 2) MiR‐188 knockout mice were resistant to aging‐associated metabolic phenotype and had higher energy expenditure, whereas adipose tissue‐specific miR‐188 transgenic mice had the opposite effects. 3) Inhibiting miR‐188 expression in BAT and iWAT of aged mice by tail vein injection of antagomiR‐188 significantly ameliorated the aging‐associated metabolic phenotype, and targeting miR‐188 might be an effective way to prevent aging‐associated metabolic dysfunction.
- Published
- 2019
19. Senescent immune cells release grancalcin to promote skeletal aging
- Author
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Xu Feng, Qi Guo, Xiang-Hang Luo, Hui Peng, Changjun Li, Min Huang, Chen He, Yu-Chen Sun, Kaixuan Chen, Tian Su, Ling Liu, Ye Xiao, Jing Hou, Mi Yang, Yan Huang, Mei Huang, Wenzhen He, and Guang-Hui Liu
- Subjects
Senescence ,Aging ,Adipogenesis ,Physiology ,Mesenchymal stem cell ,Grancalcin ,Bone Marrow Cells ,Cell Differentiation ,Mesenchymal Stem Cells ,Cell Biology ,Biology ,Rats ,Bone remodeling ,Proinflammatory cytokine ,Cell biology ,Mice ,Immune system ,medicine.anatomical_structure ,Bone Marrow ,Osteogenesis ,medicine ,Animals ,Bone marrow ,Stem cell ,Molecular Biology - Abstract
Summary Skeletal aging is characterized by low bone turnover and marrow fat accumulation. However, the underlying mechanism for this imbalance is unclear. Here, we show that during aging in rats and mice proinflammatory and senescent subtypes of immune cells, including macrophages and neutrophils, accumulate in the bone marrow and secrete abundant grancalcin. The injection of recombinant grancalcin into young mice was sufficient to induce premature skeletal aging. In contrast, genetic deletion of Gca in neutrophils and macrophages delayed skeletal aging. Mechanistically, we found that grancalcin binds to the plexin-b2 receptor and partially inactivates its downstream signaling pathways, thus repressing osteogenesis and promoting adipogenesis of bone marrow mesenchymal stromal cells. Heterozygous genetic deletion of Plexnb2 in skeletal stem cells abrogated the improved bone phenotype of Gca-knockout mice. Finally, we developed a grancalcin-neutralizing antibody and showed that its treatment of older mice improved bone health. Together, our data suggest that grancalcin could be a potential target for the treatment of age-related osteoporosis.
- Published
- 2021
20. Gender differences in a reference database of age-related femoral neck geometric parameters for Chinese population and their association with femoral neck fractures
- Author
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Hong Zhang, Meng-Lu Tang, Xian-Ping Wu, Yi-Qun Peng, Xi-Yu Wu, Xiang-Hang Luo, Ru-Chun Dai, Yi Shen, Zhi-Feng Sheng, Ling-Qing Yuan, and Er-Yuan Liao
- Subjects
Adult ,Male ,0301 basic medicine ,medicine.medical_specialty ,Histology ,Adolescent ,Physiology ,Endocrinology, Diabetes and Metabolism ,030209 endocrinology & metabolism ,Femoral Neck Fractures ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Asian People ,Confidence Intervals ,medicine ,Humans ,Aged ,Proportional Hazards Models ,Femoral neck ,Aged, 80 and over ,Bone mineral ,Sex Characteristics ,Chinese population ,Femur Neck ,business.industry ,Proportional hazards model ,Hazard ratio ,Age Factors ,Middle Aged ,Surgery ,medicine.anatomical_structure ,Databases as Topic ,Case-Control Studies ,Multivariate Analysis ,Female ,030101 anatomy & morphology ,business ,Densitometry ,Body mass index - Abstract
Femoral neck geometric parameters (FNGPs) are closely related to the strength of the femoral neck and the risk of fragility fractures. No reference database is available for FNGPs for Chinese population, and gender-related differences in FNGPs as well as their association with the risk of femoral neck fractures are unknown. This investigation aimed to set up reference databases for FNGPs, understand gender-related differences in FNGPs, and examine the association between FNGPs and the risk of osteoporotic fractures of the femoral neck. This study included 5268 females and 2156 males (aged 15-91years) from Chinese population. A total of 384 patients (282 females and 102 males) had sustained femoral neck fractures; 384 age- and sex-matched individuals without any fractures served as controls. Femoral neck DXA images were used to measure bone mineral density (BMD) and eight FNGPs. Our results showed that the age-related trends of FNGPs were fitted with the best goodness-of-fit by applying the cubic regression model. The trends shown by FNGPs were significantly different between male and female subjects, and the fitting curves were significantly higher in male subjects. After adjustments were made for age, height, weight, and body mass index, Cox regression analysis showed that changes in all FNGPs were related to increased hazard ratios (HRs) of femoral neck fractures. After further adjustment was made for BMD of the femoral neck, the HRs related to a cortical thickness (CT) decrease and buckling ratio (BR) increase in females went up by 3.35-folds (95% CI: 2.75-4.07) and 1.86-folds (95% CI: 1.33-2.60), respectively. In males, the HRs related to the decrease in CT and cross-sectional area (CSA) increased by 3.21-folds (95% CI: 2.32-4.45) and 1.88-folds (95% CI: 1.03-3.44), respectively. In conclusions, the reference databases of FNGPs established in this study will assist in the evaluation and prediction of femoral neck fracture risk in the clinic. The decrease in CT and increase in BR of the femoral neck were independent risk factors for osteoporotic fractures of the femoral neck in females from mainland China, while a decrease in CT and CSA were risk factors in male.
- Published
- 2016
21. Inhibition of cyclooxygenase-2 activity in subchondral bone modifies a subtype of osteoarthritis
- Author
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Peijian Tong, Wenlong Liu, Gehua Zhen, Manli Tu, Mei Wan, Baochao Ji, Mi Yang, Li Cao, Qiaoyue Guo, Hairong Ma, Xiang-Hang Luo, Xu Cao, and Nanxi Yu
- Subjects
0301 basic medicine ,Pathology ,medicine.medical_specialty ,Histology ,Physiology ,Endocrinology, Diabetes and Metabolism ,Transgene ,Arthritis ,Degeneration (medical) ,Osteoarthritis ,Pathogenesis ,lcsh:Physiology ,Article ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Bone ,lcsh:QH301-705.5 ,lcsh:QP1-981 ,biology ,business.industry ,medicine.disease ,3. Good health ,030104 developmental biology ,lcsh:Biology (General) ,030220 oncology & carcinogenesis ,Rheumatoid arthritis ,biology.protein ,Tumor necrosis factor alpha ,Cyclooxygenase ,business - Abstract
Osteoarthritis (OA) causes the destruction of joints. Its pathogenesis is still under investigation, and there is no effective disease-modifying therapy. Here, we report that elevated cyclooxygenase-2 (COX-2) expression in the osteocytes of subchondral bone causes both spontaneous OA and rheumatoid arthritis (RA). The knockout of COX-2 in osteocytes or treatment with a COX-2 inhibitor effectively rescues the structure of subchondral bone and attenuates cartilage degeneration in spontaneous OA (STR/Ort) mice and tumor necrosis factor-α transgenic RA mice. Thus, elevated COX-2 expression in subchondral bone induces both OA-associated and RA-associated joint cartilage degeneration. The inhibition of COX-2 expression can potentially modify joint destruction in patients with arthritis.
- Published
- 2019
22. Reducing Hypothalamic Stem Cell Senescence Protects against Aging-Associated Physiological Decline
- Author
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Changjun Li, Yu Zhong Xiao, Dongsheng Cai, Yan Huang, Qi Guo, Xiang Hang Luo, Mi Yang, and Ye Xiao
- Subjects
0301 basic medicine ,Senescence ,Aging ,Physiology ,Hypothalamus ,Biology ,Marker gene ,Catechin ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Mediator ,Neural Stem Cells ,Gallic Acid ,Animals ,Biflavonoids ,Humans ,Theaflavin ,Molecular Biology ,Cellular Senescence ,Cyclin-Dependent Kinase Inhibitor p16 ,Protein Stability ,RNA ,Cell Biology ,Phenotype ,Neural stem cell ,Cell biology ,Mice, Inbred C57BL ,030104 developmental biology ,HEK293 Cells ,chemistry ,Proteolysis ,RNA, Long Noncoding ,Y-Box-Binding Protein 1 ,Stem cell ,030217 neurology & neurosurgery ,Protein Binding - Abstract
Summary Age-dependent loss of hypothalamic neural stem cells (htNSCs) is important for the pathological consequences of aging; however, it is unclear what drives the senescence of htNSCs. Here, we report that a long non-coding RNA, Hnscr, is abundantly expressed in the htNSCs of young mice but decreases markedly in middle-aged mice. We show that depletion of Hnscr is sufficient to drive the senescence of htNSCs and aging-like phenotypes in mice. Mechanistically, Hnscr binds to Y-box protein 1 (YB-1) to prevent its degradation and thus the attenuation of transcription of the senescence marker gene p16INK4A. Through molecular docking, we discovered that a naturally occurring small compound, theaflavin 3-gallate, can mimic the activity of Hnscr. Treatment of middle-aged mice with theaflavin 3-gallate reduced the senescence of htNSCs while improving aging-associated pathology. These results point to a mediator of the aging process and one that can be pharmacologically targeted to improve aging-related outcomes.
- Published
- 2019
23. Bone Marrow Mesenchymal Stem Cells-Derived Exosomal MiR-29b-3p Regulates Aging-Associated Insulin Resistance
- Author
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Yan Huang, Tian Su, Qi Guo, Changjun Li, Fangliang Zhou, Jingxiang Wen, Yuzhong Xiao, Xiang-Hang Luo, Qiufang Deng, and Ye Xiao
- Subjects
Aging ,medicine.medical_treatment ,General Physics and Astronomy ,02 engineering and technology ,Type 2 diabetes ,010402 general chemistry ,Exosomes ,01 natural sciences ,Exosome ,Mice ,Insulin resistance ,In vivo ,Bone Marrow ,3T3-L1 Cells ,microRNA ,medicine ,Animals ,Humans ,General Materials Science ,Cells, Cultured ,Oligonucleotide Array Sequence Analysis ,biology ,Sirtuin 1 ,Chemistry ,Insulin ,General Engineering ,Mesenchymal Stem Cells ,021001 nanoscience & nanotechnology ,medicine.disease ,Microvesicles ,0104 chemical sciences ,MicroRNAs ,Cancer research ,biology.protein ,Insulin Resistance ,0210 nano-technology - Abstract
Insulin resistance is the major pathological characteristic of type 2 diabetes, and the elderly often develop insulin resistance. However, the deep-seated mechanisms for aging-related insulin resistance remain unclear. Here, we showed that nanosized exosomes released by bone marrow mesenchymal stem cells (BM-MSCs) of aged mice could be taken up by adipocytes, myocytes, and hepatocytes, resulting in insulin resistance both in vivo and in vitro. Using microRNA (miRNA) array assays, we found that the amount of miR-29b-3p was dramatically increased in exosomes released by BM-MSCs of aged mice. Mechanistically, SIRT1 (sirtuin 1) was identified to function as the downstream target of exosomal miR-29b-3p in regulating insulin resistance. Notably, utilizing an aptamer-mediated nanocomplex delivery system that down-regulated the level of miR-29b-3p in BM-MSCs-derived exosomes significantly ameliorated the insulin resistance of aged mice. Meanwhile, BM-MSCs-specific overexpression of miR-29b-3p induced insulin resistance in young mice. Taken together, these findings suggested that BM-MSCs-derived exosomal miR-29b-3p could modulate aging-related insulin resistance, which may serve as a potential therapeutic target for aging-associated insulin resistance.
- Published
- 2019
24. Krüppel-like factor 3 inhibition by mutated lncRNA
- Author
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Mi, Yang, Qi, Guo, Hui, Peng, Yu-Zhong, Xiao, Ye, Xiao, Yan, Huang, Chang-Jun, Li, Tian, Su, Yun-Lin, Zhang, Min-Xiang, Lei, Hui-Ling, Chen, Tie-Jian, Jiang, and Xiang-Hang, Luo
- Subjects
Adult ,Male ,China ,Heterozygote ,Sialoglycoproteins ,Kruppel-Like Transcription Factors ,Neovascularization, Physiologic ,Article ,Cohort Studies ,Mice ,Young Adult ,Bone Density ,Osteogenesis ,Spirostans ,Animals ,Humans ,Research Articles ,Aged ,Endothelial Progenitor Cells ,Aged, 80 and over ,Mice, Knockout ,Middle Aged ,Saponins ,Hyperostosis, Cortical, Congenital ,Mice, Inbred C57BL ,Platelet Endothelial Cell Adhesion Molecule-1 ,Osteopetrosis ,Mutation ,Female ,RNA, Long Noncoding - Abstract
The authors report a mutation in the long noncoding RNA Reg1cp that induces osteogenesis via vascular induction in humans. This mutation affects angiogenesis by blocking Klf3’s repressing activity. The Klf3 antagonist Ophiopogonin D could promote CD31hiEmcnhi vessel formation and osteogenesis in osteoporosis mice., High bone mass (HBM) is usually caused by gene mutations, and its mechanism remains unclear. In the present study, we identified a novel mutation in the long noncoding RNA Reg1cp that is associated with HBM. Subsequent analysis in 1,465 Chinese subjects revealed that heterozygous Reg1cp individuals had higher bone density compared with subjects with WT Reg1cp. Mutant Reg1cp increased the formation of the CD31hiEmcnhi endothelium in the bone marrow, which stimulated angiogenesis during osteogenesis. Mechanistically, mutant Reg1cp directly binds to Krüppel-like factor 3 (KLF3) to inhibit its activity. Mice depleted of Klf3 in endothelial cells showed a high abundance of CD31hiEmcnhi vessels and increased bone mass. Notably, we identified a natural compound, Ophiopogonin D, which functions as a KLF3 inhibitor. Administration of Ophiopogonin D increased the abundance of CD31hiEmcnhi vessels and bone formation. Our findings revealed a specific mutation in lncRNA Reg1cp that is involved in the pathogenesis of HBM and provides a new target to treat osteoporosis.
- Published
- 2018
25. Long noncoding RNA Bmncr regulates mesenchymal stem cell fate during skeletal aging
- Author
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Qi Guo, Mi Yang, Tian Su, Xiang-Hang Luo, Xi Sun, Ye Xiao, Yan Huang, and Changjun Li
- Subjects
0301 basic medicine ,Aging ,Bone Morphogenetic Protein 2 ,Bone morphogenetic protein 2 ,Extracellular matrix ,03 medical and health sciences ,Mice ,stomatognathic system ,Bone Marrow ,Osteogenesis ,medicine ,Adipocytes ,Animals ,Humans ,Skeleton ,Adiposity ,Mice, Knockout ,Adipogenesis ,Osteoblasts ,Chemistry ,Mesenchymal stem cell ,Osteoblast ,Mesenchymal Stem Cells ,General Medicine ,Cell biology ,RUNX2 ,030104 developmental biology ,medicine.anatomical_structure ,Osteoporosis ,RNA, Long Noncoding ,Bone marrow ,Fibromodulin ,Adult stem cell ,Signal Transduction ,Research Article - Abstract
Bone marrow mesenchymal stem cells (BMSCs) exhibit an age-related lineage switch between osteogenic and adipogenic fates, which contributes to bone loss and adiposity. Here we identified a long noncoding RNA, Bmncr, which regulated the fate of BMSCs during aging. Mice depleted of Bmncr (Bmncr-KO) showed decreased bone mass and increased bone marrow adiposity, whereas transgenic overexpression of Bmncr (Bmncr-Tg) alleviated bone loss and bone marrow fat accumulation. Bmncr regulated the osteogenic niche of BMSCs by maintaining extracellular matrix protein fibromodulin (FMOD) and activation of the BMP2 pathway. Bmncr affected local 3D chromatin structure and transcription of Fmod. The absence of Fmod modified the bone phenotype of Bmncr-Tg mice. Further analysis revealed that Bmncr would serve as a scaffold to facilitate the interaction of TAZ and ABL, and thus facilitate the assembly of the TAZ and RUNX2/PPARG transcriptional complex, promoting osteogenesis and inhibiting adipogenesis. Adeno-associated viral-mediated overexpression of Taz in osteoprogenitors alleviated bone loss and marrow fat accumulation in Bmncr-KO mice. Furthermore, restoring BMNCR levels in human BMSCs reversed the age-related switch between osteoblast and adipocyte differentiation. Our findings indicate that Bmncr is a key regulator of the age-related osteogenic niche alteration and cell fate switch of BMSCs.
- Published
- 2017
26. Programmed cell senescence in skeleton during late puberty
- Author
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Yu Chai, Xu Cao, Feng Quan Zhou, Changjun Li, Bin Yu, Hao Chen, Mei Wan, Lei Wang, Xiang-Hang Luo, Janet L. Crane, Bo Gao, and Peisong Gao
- Subjects
0301 basic medicine ,Senescence ,Male ,Adolescent ,Science ,General Physics and Astronomy ,Mice, Transgenic ,macromolecular substances ,Cell fate determination ,Biology ,Methylation ,General Biochemistry, Genetics and Molecular Biology ,Article ,Epigenesis, Genetic ,Histones ,Nestin ,03 medical and health sciences ,Histone H3 ,Mice ,Osteogenesis ,Animals ,Humans ,Enhancer of Zeste Homolog 2 Protein ,Sexual Maturation ,Progenitor cell ,lcsh:Science ,Cellular Senescence ,Bone growth ,Mice, Knockout ,Multidisciplinary ,Bone Development ,EZH2 ,Puberty ,Mesenchymal Stem Cells ,General Chemistry ,Cell biology ,030104 developmental biology ,Histone ,Histone methyltransferase ,biology.protein ,Osteoporosis ,lcsh:Q ,Female - Abstract
Mesenchymal stem/progenitor cells (MSPCs) undergo rapid self-renewal and differentiation, contributing to fast skeletal growth during childhood and puberty. It remains unclear whether these cells change their properties during late puberty to young adulthood, when bone growth and accrual decelerate. Here we show that MSPCs in primary spongiosa of long bone in mice at late puberty undergo normal programmed senescence, characterized by loss of nestin expression. MSPC senescence is epigenetically controlled by the polycomb histone methyltransferase enhancer of zeste homolog 2 (Ezh2) and its trimethylation of histone H3 on Lysine 27 (H3K27me3) mark. Ezh2 maintains the repression of key cell senescence inducer genes through H3K27me3, and deletion of Ezh2 in early pubertal mice results in premature cellular senescence, depleted MSPCs pool, and impaired osteogenesis as well as osteoporosis in later life. Our data reveals a programmed cell fate change in postnatal skeleton and unravels a regulatory mechanism underlying this phenomenon., Mesenchymal stem cells are essential for bone development, but it is unclear if their activity is maintained after late puberty, when bone growth decelerates. The authors show that during late puberty in mice, these cells undergo senescence under the epigenetic control of Ezh2.
- Published
- 2017
27. Lipoprotein receptor-related protein 6 is required for parathyroid hormone-inducedSostsuppression
- Author
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Mei Wan, Changjun Li, Xiang-Hang Luo, Liang Xie, Weishan Wang, and Xu Cao
- Subjects
0301 basic medicine ,Mef2 ,medicine.medical_specialty ,General Neuroscience ,Parathyroid hormone ,LRP6 ,Bone tissue ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,chemistry.chemical_compound ,030104 developmental biology ,medicine.anatomical_structure ,Endocrinology ,History and Philosophy of Science ,Downregulation and upregulation ,chemistry ,Osteocyte ,Internal medicine ,medicine ,Sclerostin ,MEF2C - Abstract
Parathyroid hormone (PTH) suppresses the expression of the bone formation inhibitor sclerostin (Sost) in osteocytes by inducing nuclear accumulation of histone deacetylases (HDACs) to inhibit the myocyte enhancer factor 2 (MEF2)-dependent Sost bone enhancer. Previous studies revealed that lipoprotein receptor-related protein 6 (LRP6) mediates the intracellular signaling activation and the anabolic bone effect of PTH. Here, we investigated whether LRP6 mediates the inhibitory effect of PTH on Sost using an osteoblast-specific Lrp6-knockout (LRP6-KO) mouse model. An increased level of Sost mRNA expression was detected in femur tissue from LRP6-KO mice, compared to wild-type littermates. The number of osteocytes expressing sclerostin protein was also increased in bone tissue of LRP6-KO littermates, indicating a negative regulatory role of LRP6 on Sost/sclerostin. In wild-type littermates, intermittent PTH treatment significantly suppressed Sost mRNA expression in bone and the number of sclerostin(+) osteocytes, while the effect of PTH was much less significant in LRP6-KO mice. Additionally, PTH-induced downregulation of MEF2C and 2D, as well as HDAC changes in osteocytes, were abrogated in LRP6-KO mice. These data indicate that LRP6 is required for PTH suppression of Sost expression.
- Published
- 2015
28. Runx2/miR-3960/miR-2861 Positive Feedback Loop Is Responsible for Osteogenic Transdifferentiation of Vascular Smooth Muscle Cells
- Author
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Hui Xie, Fei Chen, Ping-Li Xie, Xiang-Hang Luo, Zhu-Ying Xia, Er-Yuan Liao, Yin Hu, and Siyuan Tang
- Subjects
Male ,Vascular smooth muscle ,Article Subject ,Transcription, Genetic ,Myocytes, Smooth Muscle ,lcsh:Medicine ,Core Binding Factor Alpha 1 Subunit ,Biology ,Histone Deacetylases ,Muscle, Smooth, Vascular ,General Biochemistry, Genetics and Molecular Biology ,Osteogenesis ,Animals ,Myocyte ,Transcription factor ,Feedback, Physiological ,Homeodomain Proteins ,Regulation of gene expression ,Histone deacetylase 5 ,Osteoblasts ,General Immunology and Microbiology ,lcsh:R ,Transdifferentiation ,General Medicine ,musculoskeletal system ,Mice, Inbred C57BL ,RUNX2 ,MicroRNAs ,Gene Expression Regulation ,Glycerophosphates ,Cell Transdifferentiation ,Cancer research ,Research Article - Abstract
We previously reported that Runx2/miR-3960/miR-2861 regulatory feedback loop stimulates osteoblast differentiation. However, the effect of this feedback loop on the osteogenic transdifferentiation of vascular smooth muscle cells (VSMCs) remains unclear. Our recent study showed that miR-2861 and miR-3960 expression increases significantly duringβ-glycerophosphate-induced osteogenic transdifferentiation of VSMCs. Overexpression of miR-2861 or miR-3960 in VSMCs enhancesβ-glycerophosphate-induced osteoblastogenesis, whereas inhibition of miR-2861 or miR-3960 expression attenuates it. MiR-2861 or miR-3960 promotes osteogenic transdifferentiation of VSMCs by targeting histone deacetylase 5 or Homeobox A2, respectively, resulting in increased runt-related transcription factor 2 (Runx2) protein production. Furthermore, overexpression of Runx2 induces miR-2861 and miR-3960 transcription, and knockdown of Runx2 attenuatesβ-glycerophosphate-induced miR-2861 and miR-3960 transcription in VSMCs. Thus, our data show that Runx2/miR-3960/miR-2861 positive feedback loop plays an important role in osteogenic transdifferentiation of VSMCs and contributes to vascular calcification.
- Published
- 2015
29. MiR-497∼195 cluster regulates angiogenesis during coupling with osteogenesis by maintaining endothelial Notch and HIF-1α activity
- Author
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Hui Peng, Hong-Bo He, Tian Su, Man Li Tu, Tie Jian Jiang, Qi Guo, Mei Wan, Mi Yang, Xiang Hang Luo, Qiong Lu, Qing Liu, Ye Xiao, Changjun Li, Xi Sun, Xu Cao, and Min Xiang Lei
- Subjects
0301 basic medicine ,CD31 ,medicine.medical_specialty ,F-Box-WD Repeat-Containing Protein 7 ,Bone density ,Endothelium ,Angiogenesis ,Sialoglycoproteins ,Science ,Transgene ,Neovascularization, Physiologic ,General Physics and Astronomy ,Biology ,Bone and Bones ,Prolyl Hydroxylases ,Article ,General Biochemistry, Genetics and Molecular Biology ,Neovascularization ,Mice ,03 medical and health sciences ,Bone Density ,Osteogenesis ,Internal medicine ,medicine ,Animals ,Humans ,Molecular Targeted Therapy ,Receptor, Notch1 ,Receptor ,Mice, Knockout ,Multidisciplinary ,Antagomirs ,Gene Expression Regulation, Developmental ,General Chemistry ,Aptamers, Nucleotide ,Hypoxia-Inducible Factor 1, alpha Subunit ,Cell biology ,Platelet Endothelial Cell Adhesion Molecule-1 ,MicroRNAs ,030104 developmental biology ,medicine.anatomical_structure ,Endocrinology ,cardiovascular system ,Osteoporosis ,Signal transduction ,medicine.symptom ,Signal Transduction - Abstract
A specific bone vessel subtype, strongly positive for CD31 and endomucin (CD31hiEmcnhi), is identified as coupling angiogenesis and osteogenesis. The abundance of type CD31hiEmcnhi vessels decrease during ageing. Here we show that expression of the miR-497∼195 cluster is high in CD31hiEmcnhi endothelium but gradually decreases during ageing. Mice with depletion of miR-497∼195 in endothelial cells show fewer CD31hiEmcnhi vessels and lower bone mass. Conversely, transgenic overexpression of miR-497∼195 in murine endothelium alleviates age-related reduction of type CD31hiEmcnhi vessels and bone loss. miR-497∼195 cluster maintains the endothelial Notch activity and HIF-1α stability via targeting F-box and WD-40 domain protein (Fbxw7) and Prolyl 4-hydroxylase possessing a transmembrane domain (P4HTM) respectively. Notably, endothelialium-specific activation of miR-195 by intravenous injection of aptamer-agomiR-195 stimulates CD31hiEmcnhi vessel and bone formation in aged mice. Together, our study indicates that miR-497∼195 regulates angiogenesis coupled with osteogenesis and may represent a potential therapeutic target for age-related osteoporosis., H-type endothelium, defined by the high expression of CD31 and endomucin, is found in the bone where it promotes angiogenesis and osteogensis. Here Yang et al. show that the miR-497∼195 cluster regulates the generation and maintenance of the H-type endothelium by controlling the levels of Notch regulator Fbxw7 and the HIF regulator P4HTM.
- Published
- 2017
30. PDGF-BB secreted by preosteoclasts induces angiogenesis during coupling with osteogenesis
- Author
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Mei Wan, Changjun Li, Long Wang, Liang Xie, Zhuang Cui, Janet L. Crane, Weizhong Chang, Qin Bian, Bin Yu, Maureen Pickarski, Hui Xie, Xiang-Hang Luo, Gehua Zhen, Yin Hu, Zhuying Xia, Jolene J. Windle, Er-Yuan Liao, Tao Qiu, Le Thi Duong, Xu Cao, and Lingling Xian
- Subjects
CD31 ,Angiogenesis ,Cathepsin K ,Becaplermin ,Osteoclasts ,Cell Count ,Bone remodeling ,Neovascularization ,0302 clinical medicine ,Cell Movement ,Osteogenesis ,Femur ,Phosphorylation ,Tartrate-resistant acid phosphatase ,0303 health sciences ,Proto-Oncogene Proteins c-sis ,General Medicine ,3. Good health ,Isoenzymes ,Platelet Endothelial Cell Adhesion Molecule-1 ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,cardiovascular system ,Female ,medicine.symptom ,medicine.medical_specialty ,Ovariectomy ,Acid Phosphatase ,Neovascularization, Physiologic ,Biology ,Article ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,Internal medicine ,medicine ,Animals ,Protease Inhibitors ,030304 developmental biology ,Tartrate-Resistant Acid Phosphatase ,Endothelial Cells ,Mesenchymal Stem Cells ,X-Ray Microtomography ,Mice, Inbred C57BL ,Endocrinology ,Culture Media, Conditioned ,Focal Adhesion Protein-Tyrosine Kinases ,Cortical bone ,Bone marrow ,Proto-Oncogene Proteins c-akt - Abstract
Osteogenesis during bone modeling and remodeling is coupled with angiogenesis. A recent study showed that a specific vessel subtype, strongly positive for CD31 and endomucin (CD31(hi)Emcn(hi)), couples angiogenesis and osteogenesis. Here, we found that platelet-derived growth factor-BB (PDGF-BB) secreted by preosteoclasts induces CD31(hi)Emcn(hi) vessel formation during bone modeling and remodeling. Mice with depletion of PDGF-BB in the tartrate-resistant acid phosphatase-positive cell lineage show significantly lower trabecular and cortical bone mass, serum and bone marrow PDGF-BB concentrations, and fewer CD31(hi)Emcn(hi) vessels compared to wild-type mice. In the ovariectomy (OVX)-induced osteoporotic mouse model, serum and bone marrow levels of PDGF-BB and numbers of CD31(hi)Emcn(hi) vessels are significantly lower compared to sham-operated controls. Treatment with exogenous PDGF-BB or inhibition of cathepsin K to increase the number of preosteoclasts, and thus the endogenous levels of PDGF-BB, increases CD31(hi)Emcn(hi) vessel number and stimulates bone formation in OVX mice. Thus, pharmacotherapies that increase PDGF-BB secretion from preosteoclasts offer a new therapeutic target for treating osteoporosis by promoting angiogenesis and thus bone formation.
- Published
- 2014
31. MiR-503 Regulates Osteoclastogenesis via Targeting RANK
- Author
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Peng Cheng, Hou-De Zhou, Chao Chen, Hui Xie, Xian-Ping Wu, Er-Yuan Liao, and Xiang-Hang Luo
- Subjects
medicine.medical_specialty ,biology ,Chemistry ,Endocrinology, Diabetes and Metabolism ,CD14 ,Osteoporosis ,medicine.disease ,Peripheral blood mononuclear cell ,Bone resorption ,medicine.anatomical_structure ,Endocrinology ,Osteoclast ,RANKL ,Internal medicine ,medicine ,biology.protein ,Gene silencing ,Orthopedics and Sports Medicine ,Receptor - Abstract
MicroRNAs (miRNAs) play important roles in osteoclastogenesis and bone resorption. However, no study has investigated the role of miRNA in postmenopausal osteoporosis. Here, we report that miR-503 was markedly reduced in circulating progenitors of osteoclasts-CD14(+) peripheral blood mononuclear cells (PBMCs) from postmenopausal osteoporosis patients compared with those from postmenopausal healthy women. Overexpression of miR-503 in CD14(+) PBMCs inhibited receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis. Conversely, silencing of miR-503 in CD14(+) PBMCs promoted osteoclastogenesis. RANK, which is activated by the binding of RANKL and inducing osteoclast differentiation, was confirmed to be a target of miR-503. In vivo, silencing of miR-503 using a specific antagomir in ovariectomy (OVX) mice increased RANK protein expression, promoted bone resorption, and decreased bone mass, whereas overexpression of miR-503 with agomir inhibited bone resorption and prevented bone loss in OVX mice. Thus, our study revealed that miR-503 plays an important role in the pathogenesis of postmenopausal osteoporosis and contributes to a new therapeutic way for osteoporosis.
- Published
- 2014
32. Relationship between serum TGF-β1, OPG levels and osteoporotic risk in native Chinese women
- Author
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Hong-Bo He, Chao Chen, Dan-Dan Lei, Er-Yuan Liao, Hong Zhang, Jia-Ji Gong, Gen-Qing Xie, Peng Chen, Xian-Ping Wu, and Xiang-Hang Luo
- Subjects
Adult ,musculoskeletal diseases ,China ,medicine.medical_specialty ,Bone density ,Clinical Biochemistry ,Osteoporosis ,Lumbar vertebrae ,Biochemistry ,Bone remodeling ,Transforming Growth Factor beta1 ,Young Adult ,Forearm ,Osteoprotegerin ,Bone Density ,Risk Factors ,Internal medicine ,Humans ,Medicine ,Aged ,Aged, 80 and over ,Bone mineral ,business.industry ,Biochemistry (medical) ,General Medicine ,Middle Aged ,medicine.disease ,medicine.anatomical_structure ,Endocrinology ,Quartile ,Female ,business - Abstract
Background Cytokines including transforming growth factor beta 1 (TGF-β1) and osteoprotegerin (OPG) are closely related to bone metabolism. However, the relationships between TGF-β1, OPG and risk of osteoporosis in native Chinese women are unknown. Our research indicated that there is a positive correlation between TGF-β1 and bone mineral density (BMD) T-score, and a negative correlation between OPG and T-score. The risk of osteoporosis is reduced as TGF-β1 increases and increases as OPG was raised. We investigated correlations of BMD T-scores with circulating TGF-β1 and BMD T-scores with circulating OPG in healthy native Chinese women, and to study the effects of changes in TGF-β1 and OPG on osteoporosis. Methods This was a cross-sectional study of 691 healthy native Chinese women aged 20–80 years. Concentrations of serum TGF-β1 and OPG were determined. BMD T-scores at the posteroanterior spine, left hip, and forearm were measured by dual-energy X-ray absorptiometry. Results There were positive correlations between serum TGF-β1 and T-scores at the various skeletal sites (r = 0.167–0.285, all P = 0.000) and negative correlations between serum OPG and T-scores (r = − 0.179 to − 0.270, all P = 0.007–0.000). After adjusting for age and BMI, correlations between TGF-β1 and T-score at the lumbar vertebrae and ultradistal forearm, and between OPG and T-score at the ultradistal forearm in premenopausal subjects, remained statistically significant. Multivariate linear stepwise analysis showed that TGF-β1 could explain 1.9–8.3% of T-score variation at each skeletal site. OPG could explain 2.4–4.4% of T-score variation. When TGF-β1 and OPG concentrations were grouped according to quartile intervals, T-score and the prevalence and risk of osteoporosis varied with changes in the cytokines. Conclusions The risk of osteoporosis in native Chinese women increased as circulating TGF-β1 was reduced and OPG was raised.
- Published
- 2013
33. Reference intervals of bone turnover markers determined by using their curve-fitting valley for adult females in China
- Author
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Xiang-Hang Luo, Haiyan Zhang, Hui Xie, Ling-Qing Yuan, Xi-Yu Wu, Ru-Chun Dai, Er-Yuan Liao, Xian-Ping Wu, Zhi-Feng Sheng, and Yi-Qun Peng
- Subjects
Adult ,Aging ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,Reference range ,Bone remodeling ,Metabolic bone disease ,Young Adult ,Absorptiometry, Photon ,Animal science ,Asian People ,Bone Density ,Reference Values ,Internal medicine ,medicine ,Humans ,Aged ,Aged, 80 and over ,Bone mineral ,Postmenopausal women ,Anthropometry ,business.industry ,Middle Aged ,medicine.disease ,Reference intervals ,Postmenopause ,Endocrinology ,Premenopause ,Reference values ,Curve fitting ,Female ,Bone Remodeling ,business ,Biomarkers - Abstract
The reference values for bone turnover markers (BTMs) have a significant role in the diagnosis, monitoring, and treatment of metabolic bone disease. This study proposes that the peak value of bone mineral density and the trough value for the BTM curve can be used to determine the reference range of BTM. The aim of this study is to determine the reference intervals of BTMs for adult females in China with an attempt to reference the peak bone mineral density (BMD) with the corresponding BTM valley. This study included 546 premenopausal and 394 postmenopausal women. The levels of several BTMs were determined, and the BMD was measured using a dual-energy X-ray absorptiometry. The BTMs of postmenopausal women were 17–96 % higher than premenopausal women. The change of BTM with age presented an optimal goodness-of-fit according to the cubic regression model (R 2 = 0.074–0.346, all P = 0.000). All kinds of BTM levels were positively correlated with age in premenopausal women aged 27–56 years old (r = 0.167–0.502, P = 0.023–0.000). Except for uCTX, the BTM reference value determined using a curve-fitting valley was significantly lower than the reference values for premenopausal women. The BTM reference values determined in this study were also significantly different from the reference values given by the manufacturers of the reagents used. This study found that the changes of level with age of BTMs in Chinese women present an optimal goodness-of-fit according to the cubic regression model. The fitting valley corresponds to the BMD fitting peak and may possibly be an effective means of determining the BTM reference intervals.
- Published
- 2013
34. The role of microRNAs in adipocyte differentiation
- Author
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Zhu-Ying Xia, Peng Cheng, Di Wang, Hui Xie, Rong Zhang, Chao Chen, and Xiang-Hang Luo
- Subjects
Adipogenesis ,Mesenchymal stem cell ,Cell Differentiation ,General Medicine ,Biology ,Cell biology ,MicroRNAs ,chemistry.chemical_compound ,chemistry ,Adipocyte ,Medicine public health ,microRNA ,Adipocytes ,Humans ,Signal transduction ,Transcription factor ,Signal Transduction - Abstract
Adipocytes differentiate from mesenchymal stem cells (MSCs) in a process known as adipogenesis. The programme of adipogenesis is regulated by the sequential activation of transcription factors and several signaling pathways. There is growing evidence indicating that a class of small non-coding single-stranded RNAs known as "microRNAs (miRNAs)" also are involved in this process. In this review, we summarize the biology and functional mechanisms of miRNAs in adipocyte differentiation. In addition, we further discuss the miRNAs profiling, the miRNAs function and miRNAs target prediction in the adipogenesis.
- Published
- 2013
35. Early bone mineral density decrease is associated with FSH and LH, not estrogen
- Author
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Xiang-Hang Luo, Xi-Yu Wu, Shan-Jiang Yu, Hui Xie, Ling-Qing Yuan, Shiping Liu, Hong Zhang, Yi-Qun Peng, Er-Yuan Liao, Xian-Ping Wu, Zhi-Feng Sheng, and Ru-Chun Dai
- Subjects
Adult ,endocrine system ,medicine.medical_specialty ,Bone density ,medicine.drug_class ,Clinical Biochemistry ,Biochemistry ,Bone and Bones ,Body Mass Index ,Follicle-stimulating hormone ,Asian People ,Bone Density ,Internal medicine ,medicine ,Humans ,Bone mineral ,Estradiol ,business.industry ,Biochemistry (medical) ,Age Factors ,General Medicine ,Luteinizing Hormone ,Middle Aged ,medicine.disease ,Perimenopause ,Postmenopause ,Menopause ,Cross-Sectional Studies ,Endocrinology ,Premenopause ,Estrogen ,Female ,Follicle Stimulating Hormone ,Luteinizing hormone ,business ,Body mass index ,hormones, hormone substitutes, and hormone antagonists ,Hormone - Abstract
Background It remains unclear whether gonadotropins or estrogen is responsible for early bone mineral density (BMD) decrease in Chinese women. Methods A cross-sectional study was conducted on 368 healthy adult women, aged 35–60 years. We measured BMD, calculated BMD decrease rates (BDRs) and assessed serum follicle-stimulating hormone (FSH), luteinizing hormone (LH) and estradiol (E 2 ) levels. Results BDR was significantly negatively correlated with serum FSH ( r = − 0.429 to − 0.622, all p = 0.000) and LH ( r = − 0.359 to − 0.526, all p = 0.000). After adjustment for age and body mass index, the negative correlations of serum FSH and LH with BDR persisted, but there was no overall correlation between serum E 2 and BDR. Multiple linear stepwise regression analysis suggested that serum FSH is a negative determinant of BDR. Serum E 2 seems to be a positive determinant of BDR in a few parts of the skeleton. Conclusions The decrease of BMD during the menopause is associated with FSH and LH levels, rather than E 2 in Chinese women.
- Published
- 2013
36. RhoA determines lineage fate of mesenchymal stem cells by modulating CTGF–VEGF complex in extracellular matrix
- Author
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Peisong Gao, Emily Farber, Xu Cao, Liang Xie, Xiang-Hang Luo, Charles R. Farber, Mei Wan, Gehua Zhen, Yu Chai, Changjun Li, and Janet L. Crane
- Subjects
Male ,Vascular Endothelial Growth Factor A ,rho GTP-Binding Proteins ,0301 basic medicine ,RHOA ,Science ,Cellular differentiation ,General Physics and Astronomy ,Mice, Transgenic ,Article ,General Biochemistry, Genetics and Molecular Biology ,Rats, Sprague-Dawley ,Extracellular matrix ,Mice ,03 medical and health sciences ,Transforming Growth Factor beta ,Animals ,Regeneration ,Myofibroblasts ,Wound Healing ,rho-Associated Kinases ,Multidisciplinary ,biology ,Mesenchymal stem cell ,Connective Tissue Growth Factor ,Endothelial Cells ,Cell Differentiation ,Mesenchymal Stem Cells ,General Chemistry ,Extracellular Matrix ,Rats ,Cell biology ,Femoral Artery ,Mice, Inbred C57BL ,CTGF ,Vascular endothelial growth factor A ,030104 developmental biology ,Gene Expression Regulation ,biology.protein ,Matrix Metalloproteinase 3 ,Stem cell ,rhoA GTP-Binding Protein ,Wound healing ,Signal Transduction - Abstract
Mesenchymal stem cells (MSCs) participate in the repair/remodelling of many tissues, where MSCs commit to different lineages dependent on the cues in the local microenvironment. Here we show that TGFβ-activated RhoA/ROCK signalling functions as a molecular switch regarding the fate of MSCs in arterial repair/remodelling after injury. MSCs differentiate into myofibroblasts when RhoA/ROCK is turned on, endothelial cells when turned off. The former is pathophysiologic resulting in intimal hyperplasia, whereas the latter is physiological leading to endothelial repair. Further analysis revealed that MSC RhoA activation promotes formation of an extracellular matrix (ECM) complex consisting of connective tissue growth factor (CTGF) and vascular endothelial growth factor (VEGF). Inactivation of RhoA/ROCK in MSCs induces matrix metalloproteinase-3-mediated CTGF cleavage, resulting in VEGF release and MSC endothelial differentiation. Our findings uncover a novel mechanism by which cell–ECM interactions determine stem cell lineage specificity and offer additional molecular targets to manipulate MSC-involved tissue repair/regeneration., It is unclear what regulates the fate of mesenchymal stem cells (MSCs) in arterial repair following injury. Here, the authors show that MSC differentiation following injury is triggered by RhoA which in turn stimulates the release of connective tissue growth factor and vascular endothelial growth factor.
- Published
- 2016
37. GDF11 Inhibits Bone Formation by Activating Smad2/3 in Bone Marrow Mesenchymal Stem Cells
- Author
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Qiong Lu, Changjun Li, Li Zhang, T. Jiang, Xiang-Hang Luo, Man-Li Tu, and Tang Liu
- Subjects
0301 basic medicine ,Endocrinology, Diabetes and Metabolism ,Osteoporosis ,Bone Marrow Cells ,Bone healing ,Smad2 Protein ,Bone morphogenetic protein 2 ,Bone resorption ,Bone remodeling ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Endocrinology ,Osteoclast ,Osteogenesis ,medicine ,Animals ,Orthopedics and Sports Medicine ,Smad3 Protein ,Bone Resorption ,Chemistry ,Osteoblast ,Cell Differentiation ,Mesenchymal Stem Cells ,medicine.disease ,Cell biology ,Bone morphogenetic protein 7 ,Growth Differentiation Factors ,Mice, Inbred C57BL ,030104 developmental biology ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Immunology ,Bone Morphogenetic Proteins ,Female - Abstract
Growth differentiation factor 11 (GDF11) is a member of the transforming growth factor-β superfamily. Recent studies confirmed that GDF11 plays an important role in regulating the regeneration of brain, skeletal muscle, and heart during aging; however, its role in bone metabolism remains unclear. Thus, the aim of this study was to determine the effects of GDF11 on bone metabolism, including bone formation and bone resorption, both in vitro and in vivo. Our results showed that GDF11 inhibited osteoblastic differentiation of bone marrow mesenchymal stem cells in vitro. Mechanistically, GDF11 repressed Runx2 expression by inducing SMAD2/3 phosphorylation during osteoblast differentiation. Moreover, intraperitoneal injection of GDF11 inhibited bone formation and accelerated age-related bone loss in mice. Our results also showed that GDF11 had no effect on osteoclast differentiation or bone resorption both in vitro and in vivo. These results provide a further rationale for the therapeutic targeting of GDF11 for the treatment of age-related osteoporosis.
- Published
- 2016
38. miR-93/Sp7 function loop mediates osteoblast mineralization
- Author
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Hong-Bo He, Hou-De Zhou, Li Yang, Hui Xie, Gen-Qing Xie, Xian-Ping Wu, Xiang-Hang Luo, Chao Chen, and Peng Cheng
- Subjects
Chromatin Immunoprecipitation ,Endocrinology, Diabetes and Metabolism ,Regulator ,Biology ,Mice ,Transcription (biology) ,microRNA ,medicine ,Animals ,Orthopedics and Sports Medicine ,Electrophoretic mobility shift assay ,RNA, Messenger ,Sp7 Transcription Factor ,Oligonucleotide Array Sequence Analysis ,Feedback, Physiological ,Zinc finger transcription factor ,Osteoblasts ,Computational Biology ,Zinc Fingers ,Osteoblast ,Molecular biology ,Mice, Inbred C57BL ,MicroRNAs ,medicine.anatomical_structure ,Gene Expression Regulation ,Chromatin immunoprecipitation ,Transcription Factors - Abstract
microRNAs (miRNAs) play pivotal roles in osteoblast differentiation. However, the mechanisms of miRNAs regulating osteoblast mineralization still need further investigation. Here, we performed miRNA profiling and identified that miR-93 was the most significantly downregulated miRNA during osteoblast mineralization. Overexpression of miR-93 in cultured primary mouse osteoblasts attenuated osteoblast mineralization. Expression of the Sp7 transcription factor 7 (Sp7, Osterix), a zinc finger transcription factor and critical regulator of osteoblast mineralization, was found to be inversely correlated with miR-93. Then Sp7 was confirmed to be a target of miR-93. Overexpression of miR-93 in cultured osteoblasts reduced Sp7 protein expression without affecting its mRNA level. Luciferase reporter assay showed that miR-93 directly targeted Sp7 by specifically binding to the target coding sequence region (CDS) of Sp7. Experiments such as electrophoretic mobility shift assay (EMSA), chromatin immunoprecipitation (ChIP), and promoter luciferase reporter assay confirmed that Sp7 bound to the promoter of miR-93. Furthermore, overexpression of Sp7 reduced miR-93 transcription, whereas blocking the expression of Sp7 promoted miR-93 transcription. Our study showed that miR-93 was an important regulator in osteoblast mineralization and miR-93 carried out its function through a novel miR-93/Sp7 regulatory feedback loop. Our findings provide new insights into the roles of miRNAs in osteoblast mineralization. © 2012 American Society for Bone and Mineral Research.
- Published
- 2012
39. Relationship of body composition with prevalence of osteoporosis in central south Chinese postmenopausal women
- Author
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Hui Xie, Ru-Chun Dai, Xi-Yu Wu, Er-Yuan Liao, Zhi-Feng Sheng, Xin Su, Yangna Ou, Xiang-Hang Luo, Kang Xu, Ling-Qing Yuan, and Shiping Liu
- Subjects
musculoskeletal diseases ,Bone mineral ,medicine.medical_specialty ,Postmenopausal women ,business.industry ,Endocrinology, Diabetes and Metabolism ,Osteoporosis ,medicine.disease ,Menopause ,Endocrinology ,medicine.anatomical_structure ,Internal medicine ,Lean body mass ,Medicine ,Population study ,business ,Body mass index ,Femoral neck - Abstract
Summary Objectives To elucidate the relationship between body composition and bone mineral density (BMD) and the prevalence of osteoporosis in central south Chinese postmenopausal women. Methods A cross-sectional study was conducted on 954 healthy central southern Chinese postmenopausal women, aged 50–82. Total body, lumbar spine and left femur BMD and total body soft tissue composition were measured by dual X-ray absorptiometry. Results Among the study population, 578 (60·5%) subjects were without osteoporosis and 376 (39·4%) subjects were osteoporotic. The osteoporotic women were older, shorter and thinner, had an earlier age at menopause, a lower BMD and bone mineral content (BMC) of the total body and at different sites, and had lower body mass and body mass components than the women without osteoporosis. Both fat mass and lean mass were positively correlated with age at menopause, height, weight, body mass index (BMI) and BMD at all sites. Fat mass and lean mass were also inversely correlated with age and years since menopause (P
- Published
- 2011
40. Estrogen receptor α36 mediates a bone-sparing effect of 17β-estrodiol in postmenopausal women
- Author
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Hui Li, Ji-Cai Meng, Er-Yuan Liao, Mei Sun, Xiao-Bo Liao, Siyuan Tang, Dan Wang, Qi-you Wei, Hou-De Zhou, Zhi-Yong Yu, Hui Xie, Xiang-Hang Luo, Xian-Ping Wu, Zhi-Feng Sheng, Zhao-Yi Wang, Lei-Yi Zhang, and Ling-Qing Yuan
- Subjects
Adult ,MAPK/ERK pathway ,medicine.medical_specialty ,Bone density ,Endocrinology, Diabetes and Metabolism ,Osteoclasts ,Estrogen receptor ,Apoptosis ,Biology ,Bone and Bones ,Bone remodeling ,Tissue Culture Techniques ,Bone Density ,Osteogenesis ,Osteoclast ,Internal medicine ,medicine ,Humans ,Orthopedics and Sports Medicine ,RNA, Messenger ,ESTROGEN RECEPTOR α36 ,Extracellular Signal-Regulated MAP Kinases ,OSTEOBLAST ,Flavonoids ,OSTEOCLAST ,Osteoblasts ,Estradiol ,Estrogen Receptor alpha ,Osteoblast ,Middle Aged ,Enzyme Activation ,Postmenopause ,Endocrinology ,medicine.anatomical_structure ,Female ,Original Article ,Bone Remodeling ,Mitogens ,Signal transduction ,Reactive Oxygen Species ,Estrogen receptor alpha ,Biomarkers ,BONE MINERAL DENSITY - Abstract
Recently, a membrane-based estrogen receptor (ER), ER-α36, was identified and cloned that transduces membrane-initiated estrogen signaling such as activation of the mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) signaling pathway. Here we show that the postmenopausal level of estradiol (E2) induces mitogenic, antiapoptotic, and antiosteogenic effects and proapoptotic effects in postmenopausal osteoblasts and osteoclasts with high levels of ER-α36 expression, respectively. We also found that ER-α36 mediated the effects of postmenopausal-level E2 on proliferation, apoptosis, and differentiation of osteoblasts through transient activation of the MAPK/ERK pathway, whereas ER-α36-mediated postmenopausal-level E2 induces apoptosis of osteoclasts through prolonged activation of the MAPK/ERK pathway with the involvement of reactive oxygen species. We also show that the levels of ER-α36 expression in bone are positively associated with bone mineral density but negatively associated with bone biochemical markers in postmenopausal women. Thus the higher levels of ER-α36 expression are required for preserving bone mass in postmenopausal and menopausal women who become osteoporotic if ER-α36-mediated activities are dysregulated. © 2011 American Society for Bone and Mineral Research.
- Published
- 2010
41. Relationships between serum adiponectin, apelin, leptin, resistin, visfatin levels and bone mineral density, and bone biochemical markers in post-menopausal Chinese women
- Author
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Hong Zhang, Hui Xie, Xi-Yu Wu, Er-Yuan Liao, Xiang-Hang Luo, Qin Zhao, and Gen-Qing Xie
- Subjects
Adult ,Leptin ,medicine.medical_specialty ,Bone density ,Endocrinology, Diabetes and Metabolism ,Adipokine ,Bone and Bones ,Bone remodeling ,Endocrinology ,Asian People ,Bone Density ,Internal medicine ,medicine ,Humans ,Resistin ,Nicotinamide Phosphoribosyltransferase ,Aged ,Aged, 80 and over ,Bone mineral ,Adiponectin ,business.industry ,nutritional and metabolic diseases ,Middle Aged ,Apelin ,Postmenopause ,Cytokines ,Intercellular Signaling Peptides and Proteins ,Female ,business ,Biomarkers ,hormones, hormone substitutes, and hormone antagonists - Abstract
Background: Adiponectin, apelin, leptin, resistin, and visfatin, as the main circulating peptides secreted by adipose tissue, are potential contributors to bone metabolism. However, their association with bone mineral density (BMD) is unclear. Aim: The present study investigated whether these serum adipocytokines levels are associated with BMD and bone turnover markers. Methods: Serum adiponectin, apelin, leptin, resistin, visfatin levels, bone turnover biochemical markers, and BMD were determined in 336 post-menopausal Chinese women (41–81 yr old). Results: Adiponectin was negatively correlated with fat mass, while leptin had a positive correlation. In the multiple linear stepwise regression analysis, years since menopause, lean mass, estradiol, and adiponectin, but not fat mass, apelin, leptin, resistin, and visfatin, were independent predictors of BMD. The significant positive correlations between adiponectin and bone-specific alkaline phosphatase, bone cross-linked N-telopeptides of type I collagen were found. Conclusions: Adiponectin was an independent predictor of BMD in post-menopausal Chinese women, and positively correlated with bone turnover biochemical markers. It suggested that adiponectin may exert a negative effect on bone mass by promoting excessive bone resorption associated with bone loss in post-menopausal women.
- Published
- 2010
42. Suppressive effect of dexamethasone on TIMP-1 production involves murine osteoblastic MC3T3-E1 cell apoptosis
- Author
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Ling-Qing Yuan, Xiang-Hang Luo, Er-Yuan Liao, Hui Xie, Ling-Li Tang, Hou-De Zhou, Xian-Ping Wu, and Xi-Yu Wu
- Subjects
endocrine system ,medicine.medical_specialty ,Time Factors ,Clinical Biochemistry ,Mutant ,Down-Regulation ,Apoptosis ,Matrix metalloproteinase ,Biochemistry ,Dexamethasone ,Bone remodeling ,Mice ,Hormone Antagonists ,Receptors, Glucocorticoid ,Glucocorticoid receptor ,Internal medicine ,polycyclic compounds ,medicine ,Animals ,RNA, Messenger ,Bone Resorption ,RNA, Small Interfering ,Glucocorticoids ,Osteoblasts ,Tissue Inhibitor of Metalloproteinase-1 ,Dose-Response Relationship, Drug ,Caspase 3 ,Chemistry ,Organic Chemistry ,Osteoblast ,3T3 Cells ,Matrix Metalloproteinases ,Recombinant Proteins ,Mifepristone ,medicine.anatomical_structure ,Endocrinology ,Cancer research ,Mutant Proteins ,hormones, hormone substitutes, and hormone antagonists ,Glucocorticoid ,medicine.drug - Abstract
High dose glucocorticoid (GC) treatment induces osteoporosis partly via increasing osteoblast apoptosis. However, the mechanism of GC-induced apoptosis has not been fully elucidated. Osteoblast-derived tissue inhibitor of metalloproteinase-1 (TIMP-1) was recently reported to be involved in bone metabolism. Our previous study demonstrated that TIMP-1 suppressed apoptosis of the mouse bone marrow stromal cell line MBA-1 (pre-osteoblast) induced by serum deprivation. Therefore, we tested the effect of the GC dexamethasone (Dex) on TIMP-1 production in murine osteoblastic MC3T3-E1 cells and further determined whether this action is associated with Dex-induced osteoblast apoptosis. Dex decreased TIMP-1 production in MC3T3-E1 cells, and this effect was blocked by the glucocorticoid receptor (GR) antagonists, RU486 and RU40555. Recombinant TIMP-1 protein reduced caspase-3 activation and apoptosis induced by Dex in MC3T3-E1 cells. In addition, the pro-apoptotic effect of the Dex was augmented by suppression of TIMP-1 with siRNA. Furthermore, mutant TIMP-1, which has no inhibitory effects on MMPs, yet protects MC3T3-E1 cells against Dex-induced apoptosis. Our study demonstrates that Dex suppresses TIMP-1 production in osteoblasts through GR, and this effect is associated with its induction of osteoblast apoptosis. The anti-apoptotic action of TIMP-1 is independent of its inhibitory effects on MMPs activities. The decrease in TIMP-1 production caused by Dex may contribute to the mechanisms of Dex-induced bone loss.
- Published
- 2009
43. Age-related changes in biochemical markers of bone turnover and gonadotropin levels and their relationship among Chinese adult women
- Author
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Hong Zhang, Xian-Ping Wu, Xi-Yu Wu, Yi-Qun Peng, Er-Yuan Liao, Xiang-Hang Luo, Hui Xie, Xin Su, and Ling-Qing Yuan
- Subjects
Adult ,Aging ,endocrine system ,medicine.medical_specialty ,medicine.drug_class ,Endocrinology, Diabetes and Metabolism ,Osteoporosis ,Bone resorption ,Bone remodeling ,Young Adult ,Follicle-stimulating hormone ,Internal medicine ,Humans ,Medicine ,Young adult ,Aged ,Aged, 80 and over ,Anthropometry ,business.industry ,Luteinizing Hormone ,Middle Aged ,medicine.disease ,Cross-Sectional Studies ,Endocrinology ,Female ,Bone Remodeling ,Follicle Stimulating Hormone ,Menopause ,Gonadotropin ,business ,Luteinizing hormone ,Biomarkers ,Hormone - Abstract
The relationship between the levels of gonadotropic hormones and bone metabolism in Chinese adult women is unclear. Our research shows that a significant positive correlation exists between the levels of gonadotropic hormones and various bone turnover indicators. Follicle-stimulating hormone (FSH) has been found to have a greater influence on all types of bone turnover indicator than luteinizing hormone (LH). Further, FSH has a greater influence on bone formation indicators than on bone resorption indicators.The aim of this study was to investigate the relationship between serum FSH and LH and biochemical markers of bone turnover in native Chinese adult women.We conducted a cross-sectional study of 694 healthy Chinese women aged between 20 and 82 years. Serum FSH, LH, bone-specific alkaline phosphatase (BAP), osteocalcin (OC), N-terminal telopeptides of type I collagen, C-terminal telopeptides of type I collagen, urinary NTX, urinary CTX, and urinary deoxypyridinoline (uDPD) were determined.All types of bone turnover indicator were significantly positively correlated with FSH (r = 0.164-0.626, all P = 0.000) and LH (r = 0.130-0.618, all P = 0.013-0.000). The correlation coefficient between serum FSH and BAP was the highest (r = 0.626), and that between serum FSH and uDPD was the lowest (r = 0.164). The serum gonadotropic hormone levels were higher; concentrations of bone turnover indicators were higher. The extent of the influence of FSH on various bone turnover indicators was approximately seven to 20 times greater than that of LH on these indicators. FSH could explain 43% and 22% of the changes in BAP and OC, respectively; whereas, LH could explain only 2.1% and 1.1%, respectively. FSH could explain approximately 1.9-11.8% of the changes in bone resorption indicators; however, LH had almost no effect on them.Gonadotropic hormone levels are correlated with the rate of bone turnover in Chinese women: the higher the serum gonadotropic hormone levels in circulation, the higher the levels of bone turnover indicators. FSH has a greater influence on all types of bone turnover indicator than LH; moreover, it has a greater influence on bone formation indicators than on bone resorption indicators.
- Published
- 2009
44. Connective tissue growth factor is a downstream mediator for preptin-induced proliferation and differentiation in human osteoblasts
- Author
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You-Shuo Liu, Hui Xie, Wei Liu, Xiang-Hang Luo, Ling-Qing Yuan, Er-Yuan Liao, Ying Lu, and Xian-Ping Wu
- Subjects
MAPK/ERK pathway ,medicine.medical_specialty ,Time Factors ,p38 mitogen-activated protein kinases ,medicine.medical_treatment ,Cellular differentiation ,Clinical Biochemistry ,Biology ,Biochemistry ,Bone and Bones ,Bone remodeling ,Downregulation and upregulation ,Insulin-Like Growth Factor II ,Internal medicine ,medicine ,Humans ,Phosphorylation ,RNA, Small Interfering ,Extracellular Signal-Regulated MAP Kinases ,Cells, Cultured ,Cell Proliferation ,Osteoblasts ,Growth factor ,Organic Chemistry ,Connective Tissue Growth Factor ,Cell Differentiation ,Alkaline Phosphatase ,Peptide Fragments ,Recombinant Proteins ,Up-Regulation ,Cell biology ,Enzyme Activation ,CTGF ,Endocrinology ,Signal transduction ,Signal Transduction - Abstract
Preptin, a newly isolated 34-amino-acid peptide hormone that is cosecreted with insulin and amylin from pancreatic beta-cells, has emerged as a regulatory element in bone metabolism, but its mechanism remains unclear. We assessed the effects of preptin on proliferation and differentiation of human osteoblasts and investigated the mechanism involved. Our results demonstrated that preptin promoted human osteoblasts proliferation and alkaline phosphatase activity. Suppression of connective tissue growth factor (CTGF), which was upregulated by preptin in a dose- and time-dependent manner, with small interfering RNA (siRNA) abolished the preptin-induced human osteoblasts proliferation and differentiation. Preptin induced activation of ERK mitogen-activated protein kinase (MAPK), but not p38 or JNK in human osteoblasts. Furthermore, pretreatment of human osteoblasts with the ERK inhibitor PD98059 abolished the preptin-induced CTGF secretion and blocked the promoting effect of preptin on osteoblasts proliferation and differentiation. These data demonstrated that preptin is involved in bone anabolism mediated by ERK/CTGF in human osteoblasts and may contribute to the preservation of bone mass observed in hyperinsulinemic states, such as obesity.
- Published
- 2009
45. Effect of progesterone on apoptosis of murine MC3T3-E1 osteoblastic cells
- Author
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Xiang-Hang Luo, Ling-Qing Yuan, Hui Li, Dan Wang, Ping Meng, Qing-Ping Wang, Hui Xie, and Er-Yuan Liao
- Subjects
Clinical Biochemistry ,Apoptosis ,Biology ,Biochemistry ,Culture Media, Serum-Free ,Cell Line ,Substrate Specificity ,Mice ,chemistry.chemical_compound ,Western blot ,Progesterone receptor ,medicine ,Animals ,Protein Isoforms ,Progesterone ,chemistry.chemical_classification ,Osteoblasts ,medicine.diagnostic_test ,Caspase 3 ,Cytochrome c ,Organic Chemistry ,Osteoblast ,Molecular biology ,Caspase 9 ,In vitro ,Enzyme ,medicine.anatomical_structure ,chemistry ,biology.protein ,Receptors, Progesterone ,Ethidium bromide - Abstract
Progesterone (P) has been suggested as a bone-trophic hormone. Previous studies have shown that P promoted bone formation by stimulating the proliferation and differentiation of osteoblasts. But, the effect of P on apoptosis of osteoblast in vitro has not been reported. We propose that P may promote bone formation by suppressing the apoptosis of osteoblast. The present study was performed to investigate the effect of P on apoptosis of murine MC3T3-E1 osteoblastic cells. Cell apoptosis was measured by acidine orange/ethidium bromide (AO/EB) staining and sandwich-enzyme-immunoassay. Progesterone receptor (PR), cytochrome c, caspase-9 and caspase-3 protein levels were determined by Western blot analysis. The enzyme substrate was also used to assess the activation of caspase-3 and caspase-9. Progesterone suppressed MC3T3-E1 cells apoptosis induced by serum deprivation, and this effect was blocked by a PR antagonist RU486. Furthermore, the suppressive effects of P on cytochrome c release and caspase-9 and caspase-3 activation in serum-deprived MC3T3-E1 cells were also reversed by RU486. Our study demonstrated that P protects osteoblast against apoptosis through PR and the downstream mitochondrial pathway. Thus, the data suggest that the effects of P on osteoblast apoptosis may contribute to the mechanisms by which P exerts its action on bone formation.
- Published
- 2008
46. Recombinant tissue metalloproteinase inhibitor-3 protein induces apoptosis of murine osteoblast MC3T3-E1
- Author
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Hui Xie, Li-Juan Guo, Er-Yuan Liao, Ling-Qing Yuan, Xi-Yu Wu, Ying Lu, You-Shuo Liu, and Xiang-Hang Luo
- Subjects
MAPK/ERK pathway ,Fas Ligand Protein ,MAP Kinase Signaling System ,Pyridines ,p38 mitogen-activated protein kinases ,Clinical Biochemistry ,Apoptosis ,Matrix metalloproteinase ,Biology ,Biochemistry ,Gene Expression Regulation, Enzymologic ,Fas ligand ,Cell Line ,Mice ,Western blot ,medicine ,Animals ,Humans ,fas Receptor ,Enzyme Inhibitors ,Phosphorylation ,Flavonoids ,Mitogen-Activated Protein Kinase Kinases ,Tissue Inhibitor of Metalloproteinase-3 ,Inhibitor of apoptosis domain ,Caspase 8 ,Osteoblasts ,medicine.diagnostic_test ,Caspase 3 ,Organic Chemistry ,Imidazoles ,Molecular biology ,Recombinant Proteins ,Signal transduction - Abstract
Tissue inhibitor of metalloproteinases (TIMPs) plays an essential role in the regulation of bone metabolism. Here we report that recombinant tissue metalloproteinase inhibitor-3 (TIMP-3) protein induces the apoptosis of MC3T3-E1 osteoblasts. Cell apoptosis was detected by sandwich-enzyme-immunoassay. Fas and Fasl protein levels were determined by Western blot analysis. The enzyme substrate was used to assess the activation of caspase-3 and caspase-8. The phosphorylation of JNK, p38 and ERK1/2 was examined by Western blot analysis. The ELISA suggested that TIMP-3 promoted MC3T3-E1 cell apoptosis. TIMP-3 treatment induced the expression of Fas and Fasl proteins, and the activation of caspase-8 and caspase-3. TIMP-3 treatment induced p38 and ERK phosphorylation. SB203580 and PD98059, the inhibitor of p38 and ERK, respectively, abolished the TIMP-3 effect on osteoblast apoptosis. In conclusion, the signal pathway through which TIMP-3 induces MC3T3-E1 cell apoptosis, mediated by Fas and involves the p38 and ERK signal transduction pathways.
- Published
- 2007
47. WISP3 suppresses insulin-like growth factor signaling in human chondrocytes
- Author
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Er-Yuan Liao, Jiao Huang, Xiang-Hang Luo, Hou-De Zhou, Ling-Qing Yuan, Rong-Rong Cui, Lu Yi, Yi-Qun Peng, Min Wang, and Hui Xie
- Subjects
MAPK/ERK pathway ,medicine.medical_specialty ,medicine.medical_treatment ,Biochemistry ,Insulin-like growth factor-binding protein ,Cell Line ,Receptor, IGF Type 1 ,CCN Intercellular Signaling Proteins ,Insulin-like growth factor ,Chondrocytes ,Endocrinology ,Downregulation and upregulation ,Internal medicine ,medicine ,Humans ,Insulin-Like Growth Factor I ,Molecular Biology ,biology ,Chemistry ,Cartilage ,Growth factor ,Recombinant Proteins ,Up-Regulation ,Cell biology ,Insulin-Like Growth Factor Binding Proteins ,medicine.anatomical_structure ,Mutation ,biology.protein ,Collagen ,Signal transduction ,Signal Transduction - Abstract
WISP3 is essential for maintaining cartilage integrity mainly by regulating the expression of collagen II, and mutations of WISP3 linked to spondyloepiphyseal dysplasia tarda with progressive arthropathy (SEDT-PA) can compromise this function and lead to cartilage loss. The aim of this study was to evaluate the effect of WISP3 on insulin-like growth factor (IGF) signaling in human chondrocytes, investigate whether WISP3 up-regulates collagen II through the IGF signaling pathway, and compare IGF signaling between wild-type and mutant WISP3. Experimental results suggest that WISP3 up-regulates collagen II expression and inhibits the activation of IGF-IR, IRS-1, and ERK kinase in human chondrocytes, and mutation of WISP3 augments IGF signaling in human chondrocytes. In addition to the IGF signaling pathway, WISP3 might up-regulate collagen II expression through an IGF-independent signaling cascade.
- Published
- 2007
48. l-Carnitine protects against apoptosis of murine MC3T3-E1 osteoblastic cells
- Author
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Hui Xie, Er-Yuan Liao, Hong-Li Li, Siyuan Tang, Dan Wang, Ling-Qing Yuan, and Xiang-Hang Luo
- Subjects
Blotting, Western ,Clinical Biochemistry ,Apoptosis ,Mitochondrion ,Biology ,Biochemistry ,Dexamethasone ,Cell Line ,Mice ,Structure-Activity Relationship ,Western blot ,Carnitine ,medicine ,Animals ,bcl-2-Associated X Protein ,chemistry.chemical_classification ,Osteoblasts ,Dose-Response Relationship, Drug ,medicine.diagnostic_test ,Cytochrome c ,Organic Chemistry ,Cytochromes c ,Osteoblast ,Metabolism ,Molecular biology ,Culture Media ,Cytosol ,medicine.anatomical_structure ,Enzyme ,Proto-Oncogene Proteins c-bcl-2 ,chemistry ,Caspases ,biology.protein - Abstract
L-carnitine (LC), an amino acid with a major role in cellular energy metabolism, has positive effects on bone metabolism. However, the effect of LC on apoptosis of osteoblast in vitro has not been reported. The aim of this study was to investigate the action of LC on apoptosis of mouse osteoblastic cell line MC3T3-E1. Cell apoptosis was measured by sandwich-enzyme-immunoassay. Release of cytochrome c from mitochondria into cytosol and Bcl-2, Bax protein levels were determined by Western blot analysis. The enzyme substrate was used to assess the activation of caspase-3 and caspase-9. LC inhibited MC3T3-E1 cell apoptosis induced by serum deprivation. Our study also shows that LC decreased cytochrome c release and caspase-3 and caspase-9 activation in serum-deprived MC3T3-E1 cells. Furthermore, LC protected against MC3T3-E1 cell apoptosis induced by the glucocorticoid (GC) dexamethasone (Dex).
- Published
- 2007
49. Effects of the sample size of reference population on determining BMD reference curve and peak BMD and diagnosing osteoporosis
- Author
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Ru-Chun Dai, Er-Yuan Liao, Yan-Li Hou, Xing-Zhi Cao, Xiang-Hang Luo, Xi-Yu Wu, Yi-Qun Peng, and Haiyan Zhang
- Subjects
Adult ,musculoskeletal diseases ,medicine.medical_specialty ,Adolescent ,Bone density ,Endocrinology, Diabetes and Metabolism ,Osteoporosis ,Asian People ,Bone Density ,Reference Values ,Statistics ,Humans ,Medicine ,Reference population ,Child ,Aged ,Aged, 80 and over ,Bone mineral ,business.industry ,Reproducibility of Results ,Middle Aged ,medicine.disease ,Surgery ,Large sample ,Sample size determination ,Sample Size ,Reference values ,Regression Analysis ,Female ,business ,Densitometry - Abstract
Establishing reference databases generally requires a large sample size to achieve reliable results. Our study revealed that the varying sample size from hundreds to thousands of individuals has no decisive effect on the bone mineral density (BMD) reference curve, peak BMD, and diagnosing osteoporosis. It provides a reference point for determining the sample size while establishing local BMD reference databases.This study attempts to determine a suitable sample size for establishing bone mineral density (BMD) reference databases in a local laboratory.The total reference population consisted of 3,662 Chinese females aged 6-85 years. BMDs were measured with a dual-energy X-ray absorptiometry densitometer. The subjects were randomly divided into four different sample groups, that is, total number (Tn) = 3,662, 1/2n = 1,831, 1/4n = 916, and 1/8n = 458. We used the best regression model to determine BMD reference curve and peak BMD.There was no significant difference in the full curves between the four sample groups at each skeletal site, although some discrepancy at the end of the curves was observed at the spine. Peak BMDs were very similar in the four sample groups. According to the Chinese diagnostic criteria (BMD25% below the peak BMD as osteoporosis), no difference was observed in the osteoporosis detection rate using the reference values determined by the four different sample groups.Varying the sample size from hundreds to thousands has no decisive effect on establishing BMD reference curve and determining peak BMD. It should be practical for determining the reference population while establishing local BMD databases.
- Published
- 2007
50. Differences in age-related bone mass of proximal femur between Chinese women and different ethnic women in the United States
- Author
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Er-Yuan Liao, Yue-xia Jiang, Yan-Li Hou, Hong Zhang, Xian-Ping Wu, Xing-Zhi Cao, and Xiang-Hang Luo
- Subjects
Adult ,Gerontology ,Aging ,China ,medicine.medical_specialty ,National Health and Nutrition Examination Survey ,Endocrinology, Diabetes and Metabolism ,Random Allocation ,Endocrinology ,Bone Density ,Epidemiology ,Humans ,Medicine ,Orthopedics and Sports Medicine ,Femur ,Aged ,Femoral neck ,Aged, 80 and over ,Bone mineral ,business.industry ,Bone age ,General Medicine ,Middle Aged ,medicine.disease ,United States ,Osteopenia ,medicine.anatomical_structure ,Orthopedic surgery ,Osteoporosis ,Female ,business ,Demography - Abstract
Substantial racial differences in bone mass and bone loss rate have been reported, but the extent of the difference between native Chinese women and women of different races in the United States is not clear. We used a DXA bone densitometer to measure bone mineral density (BMD), bone mineral content (BMC), bone area (BA), and volumetric BMD (vBMD) in different regions of the proximal femur in 3614 Chinese women aged 20 years and older. Regression models were chosen to best fit the changes of these parameters with increasing age. The values in their fitted curves were determined by the Cartesian coordinate numeration system. Subsequently, we compared these fitted curves to full-matched data of non-Hispanic black, non-Hispanic white, and Mexican American women reported by the third National Health and Nutrition Examination Survey (NHANES III). We found that all fitted curves of bone mass of non-Hispanic black women were significantly higher than those of Chinese, non-Hispanic white, and Mexican American women (P = 0.000). The BMD and BMC fitted curves in various regions of the hip for non-Hispanic blacks were 22%-28% and 26%-43% higher than those for Chinese women, 8.3%-13% and 7.9%-9.5% higher than those for non-Hispanic whites, and 8.8%-10% and 13%-19% higher than those for Mexican Americans, respectively. However, when the expression of difference was transformed from BMD to vBMD at the femoral neck, the difference between Chinese and non-Hispanic black women was reduced from 22% to 18% and that between Chinese and non-Hispanic white women from 7.4% to 0.8%, but the difference increased from 3.2% to 9.6% between non-Hispanic white and Mexican American women and from 13% to 17% between non-Hispanic white and non-Hispanic black women. By the age of 80 years, the accumulated bone loss rate in various regions of the proximal femur for Chinese, Mexican Americans, non-Hispanic whites, and non-Hispanic blacks were -38.9% +/- 1.8%, -34.4% +/- 3.1%, -27.8% +/- 5.9%, and -28.4% +/- 4.8%, respectively. In conclusion, bone mass in the proximal femur of native Chinese women is significantly lower, and the bone loss rate greater, than those of non-Asian women in the United States. At the femoral neck, the vBMD of Chinese women is similar to that of non-Hispanic white women.
- Published
- 2007
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