8 results on '"Jian Q. Feng"'
Search Results
2. Constitutive Nuclear Expression of Dentin Matrix Protein 1 Fails to Rescue the Dmp1-null Phenotype.
- Author
-
Shuxian Lin, Qi Zhang, Zhengguo Cao, Yongbo Lu, Hua Zhang, Kevin Yan, Ying Liu, McKee, Marc D., Chunlin Qin, Zhi Chen, and Jian Q. Feng
- Subjects
- *
DENTIN , *PHENOTYPES , *EXTRACELLULAR matrix proteins , *HOMEOSTASIS , *PROTEIN kinases , *OSTEOBLASTS - Abstract
Dentin matrix protein 1 (DMP1) plays multiple roles in bone, tooth, phosphate homeostasis, kidney, salivary gland, reproductive cycles, and the development of cancer. In vitro studies have indicated two different biological mechanisms: 1) as a matrix protein, DMP1 interacts with αvβ3 integrin and activates MAP kinase signaling; and 2) DMP1 serves as a transcription co-factor. In vivo studies have demonstrated its key role in osteocytes. This study attempted to determine whether DMP1 functions as a transcription co-factor and regulates osteoblast functions. For gene expressioncomparisons using adenovirus constructs, we targeted the expression of DMP1 either to the nucleus only by replacing the endogenous signal peptide with a nuclear localization signal (NLS) sequence (referred to as NLSDMP1) or to the extracellular matrix as the WT type (referred to as (SP)DMP1) in MC3T3 osteoblasts. High levels of DMP1 in either form greatly increased osteogenic gene expression in an identical manner. However, the targeted NLSDMP1 transgene driven by a 3.6-kb rat Col 1α1 promoter in the nucleus of osteoblasts and osteocytes failed to rescue the phenotyope of Dmp1-null mice, whereas the (SP)DMP1 transgene rescued the rickets defect. These studies support the notion that DMP1 functions as an extracellularmatrix protein, rather than as a transcription co-factor in vivo. We also show that DMP1 continues its expression in osteoblasts during postnatal development and that the deletion of Dmp1 leads to an increase in osteoblast proliferation. However, poor mineralization in the metaphysis indicates a critical role for DMP1 in both osteoblasts and osteocytes. [ABSTRACT FROM AUTHOR] more...
- Published
- 2014
- Full Text
- View/download PDF
Catalog
3. Cessation of Epithelial Bmp Signaling Switches the Differentiation of Crown Epithelia to the Root Lineage in a β-Catenin-Dependent Manner.
- Author
-
Zhenhua Yang, Bo Hai, Lizheng Qin, Xinyu Ti, Lei Shangguan, Yanqiu Zhao, Wiggins, Lindsey, Ying Liu, Jian Q. Feng, Yu Fong Chang, Julia, Fen Wang, and Fei Liu
- Subjects
- *
EPITHELIAL cells , *CELL differentiation , *DENTAL crowns , *AMELOBLASTS , *CELL determination - Abstract
The differentiation of dental epithelia into enamel-producing ameloblasts or the root epithelial lineage compartmentalizes teeth into crowns and roots. Bmp signaling has been linked to enamel formation, but its role in root epithelial lineage differentiation is unclear. Here we show that cessation of epithelial Bmp signaling by Bmpr1a depletion during the differentiation stage switched differentiation of crown epithelia into the root lineage and led to formation of ectopic cementum-like structures. This phenotype is related to the upregulation of Wnt/β-catenin signaling and epithelial-mesenchymal transition (EMT). Although epithelial β-catenin depletion during the differentiation stage also led to variable enamel defect and precocious/ectopic formation of fragmented root epithelia in some teeth, it did not cause ectopic cementogenesis and inhibited EMT in cultured dental epithelia. Concomitant epithelial β-catenin depletion rescued EMT and ectopic cementogenesis caused by Bmpr1a depletion. These data suggested that Bmp and Wnt/β-catenin pathways interact antagonistically in dental epithelia to regulate the root lineage differentiation and EMT. These findings will aid in the design of new strategies to promote functional differentiation in the regeneration and tissue engineering of teeth and will provide new insights into the dynamic interactions between the Bmp and Wnt/β-catenin pathways during cell fate decisions. [ABSTRACT FROM AUTHOR] more...
- Published
- 2013
- Full Text
- View/download PDF
4. The Rescue of Dentin Matrix Protein 1 (DMP1)-deficient Tooth Defects by the Transgenic Expression of Dentin Sialophosphoprotein (DSPP) Indicates That DSPP Is a Downstream Effector Molecule of DMP1 in Dentinogenesis.
- Author
-
Gibson, Monica Prasad, Qinglin Zhu, Suzhen Wang, Qilin Liu, Ying Liu, Xiaofang Wang, Baozhi Yuan, Ruest, L. Bruno, Jian Q. Feng, D'Souza, Rena N., Chunlin Qin, and Yongbo Lu
- Subjects
- *
DENTINOGENESIS , *EXTRACELLULAR matrix proteins , *CELL culture , *ODONTOBLASTS , *GENE expression - Abstract
Dentin matrix protein 1 (DMP1) and dentin sialophosphoprotein (DSPP) are essential for the formation of dentin. Previous in vitro studies have indicated that DMP1 might regulate the expression of DSPP during dentinogenesis. To examine whether DMP1 controls dentinogenesis through the regulation of DSPP in vivo, we cross-bred transgenic mice expressing normal DSPP driven by a 3.6-kb rat Col1a1 promoter with Dmp1 KO mice to generate mice expressing the DSPP transgene in the Dmp1 KO genetic background (referred to as "Dmp1 KO/DSPP Tg mice"). We used morphological, histological, and biochemical techniques to characterize the dentin and alveolar bone of Dmp1 KO/DSPP Tg mice compared with Dmp1 KO and wild-type mice. Our analyses showed that the expression of endogenous DSPP was remarkably reduced in the Dmp1 KO mice. Further more, the transgenic expression of DSPP rescued the toot hand alveolar bone defects of the Dmp1 KO mice. In addition, our in vitro analyses showed that DMP1 and its 57-kDaC-terminal fragment significantly up-regulated the Dspp promoter activities in a mesenchymal cell line. In contrast, the expression of DMP1 was not altered in the Dspp KO mice. These results provide strong evidence that DSPP is a downstream effector molecule that mediates the roles of DMP1 in dentinogenesis. [ABSTRACT FROM AUTHOR] more...
- Published
- 2013
- Full Text
- View/download PDF
5. The Growth Factor Progranulin Binds to TNF Receptors and Is Therapeutic Against Inflammatory Arthritis in Mice.
- Author
-
Wei Tang, Yi Lu, Qing-Yun Tian, Yan Zhang, Feng-Jin Guo, Guang-Yi Liu, Syed, Nabeel Muzaffar, Yongjie Lai, Lin, Edward Alan, Li Kong, Su, Jeffrey, Fangfang Yin, Ai-Hao Ding, Zanin-Zhorov, Alexandra, Dustin, Michael L., Jian Tao, Craft, Joseph, Zhinan Yin, Jian Q. Feng, and Abramson, Steven B. more...
- Subjects
- *
GROWTH factors , *TUMOR necrosis factors , *INFLAMMATION , *ARTHRITIS , *LABORATORY mice , *COLLAGEN , *ETIOLOGY of diseases - Abstract
The growth factor progranulin (PGRN) has been implicated in embryonic development, tissue repair, tumorigenesis, and inflammation, but its receptors remain unidentified. We report that PGRN bound directly to tumor necrosis factor receptors (TNFRs) and disturbed the TNFα-TNFR interaction. PGRN-deficient mice were susceptible to collagen-induced arthritis, and administration of PGRN reversed inflammatory arthritis. Atsttrin, an engineered protein composed of three PGRN fragments, exhibited selective TNFR binding. PGRN and Atsttrin prevented inflammation in multiple arthritis mouse models and inhibited TNFα-activated intracellular signaling. Collectively, these findings demonstrate that PGRN is a ligand of TNFR, an antagonist of TNFα signaling, and plays a critical role in the pathogenesis of inflammatory arthritis in mice. They also suggest new potential therapeutic interventions for various TNFα-mediated pathologies and conditions, including rheumatoid arthritis. [ABSTRACT FROM AUTHOR] more...
- Published
- 2011
- Full Text
- View/download PDF
6. Periostin Null Mice Exhibit Dwarfism, Incisor Enamel Defects, and an Early-Onset Periodontal Disease-Like Phenotype.
- Author
-
Rios, Hector, Koushik, Shrinagesh V., HaiyanWang, Jian Wang, Hong-Ming Zhou, Lindsley, Andrew, Rogers, Rhonda, Zhi Chen, Maeda, Manabu, Kruzynska-Frejtag, Agnieszka, Jian Q. Feng, and Conway, Simon J. more...
- Subjects
- *
LIGAMENTS , *PHENOTYPES , *PERIODONTAL ligament , *PERIODONTAL disease , *LABORATORY rats , *GENOTYPE-environment interaction , *GROWTH disorders , *PERIODONTICS - Abstract
Periostin was originally identified as an osteoblast-specific factor and is highly expressed in the embryonic periosteum, cardiac valves, placenta, and periodontal ligament as well as in many adult cancerous tissues. To investigate its role during development, we generated mice that lack the periostin gene and replaced the translation start site and first exon with a lacZ reporter gene. Surprisingly, although periostin is widely expressed in many developing organs, periostin-deficient (perilacZ) embryos are grossly normal. Postnatally, however, ∼14% of the nulls die before weaning and all of the remaining perilacZ nulls are severely growth retarded. Skeletal analysis revealed that trabecular bone in adult homozygous skeletons was sparse, but overall bone growth was unaffected. Furthermore, by 3 months, the nulls develop an early-onset periodontal disease-like phenotype. Unexpectedly, these mice also show a severe incisor enamel defect, although there is no apparent change in ameloblast differentiation. Significantly, placing the perilacZ nulls on a soft diet that alleviated mechanical strain on the periodontal ligament resulted in a partial rescue of both the enamel and periodontal disease-like phenotypes. Combined, these data suggest that a healthy periodontal ligament is required for normal amelogenesis and that periostin is critically required for maintenance of the integrity of the periodontal ligament in response to mechanical stresses. [ABSTRACT FROM AUTHOR] more...
- Published
- 2005
- Full Text
- View/download PDF
7. Differential Regulation of Dentin Matrix Protein 1 Expression during Odontogenesis.
- Author
-
Yongbo Lu, Shubin Zhang, Yixia Xie, Yuli Pi, and Jian Q. Feng
- Subjects
- *
DENTIN , *PROTEINS , *TEETH , *ODONTOGENIC cysts , *GENES - Abstract
Dentin matrix protein 1 (DMP1) is highly expressed in mineralized tooth and bone. Both in vitroand in vivodata show that DMP1 is critical for mineralization and tooth morphogenesis (growth and development). In this study, we studied Dmp1 gene regulation. The in vitrotransient transfection assay identified two important DNA fragments, the 2.4- and 9.6-kb promoter regions. We next generated and analyzed transgenic mice bearing the β-galactosidase (lacZ) reporter gene driven by the 2.4- or 9.6-kb promoter with the complete 4-kb intron 1. The 9.6-kb Dmp1-lacZ mice conferred a DMP1 expression pattern in odontoblasts identical to that in the endogenous Dmp1 gene. This is reflected by lacZ expression in Dmp1-lacZ knock-in mice during all stages of odontogenesis. In contrast, the 2.4-kb Dmp1-lacZ mice display activity in odontoblast cells only at the early stage of odontogenesis. Thus, we propose that different transcription factors regulate early or later cis-regulatory domains of the Dmp1 promoter, which gives rise to the unique spatial and temporal expression pattern of Dmp1 gene at different stages of tooth development. Copyright © 2005 S. Karger AG, Basel [ABSTRACT FROM AUTHOR] more...
- Published
- 2005
- Full Text
- View/download PDF
8. Dentin Matrix Protein 1 Gene Cis-regulation.
- Author
-
Wuchen Yang, Yongbo Lu, Kalajzic, Ivo, Dayong Guo, Harris, Marie A., Gluhak-Heinrich, Jelica, Kotha, Shiva, Bonewald, Lynda F., Jian Q. Feng, Rowe, David W., Turner, Charles H., Robling, Alexander G., and Harris, Stephen E. more...
- Subjects
- *
EXTRACELLULAR matrix proteins , *OSTEOCYTES , *BONE cells , *GENE expression , *DENDRITIC cells , *ANTIGEN presenting cells , *LYMPHOID tissue - Abstract
Dentin matrix protein 1 (DMP1) is highly expressed in osteocytes and is mechanically responsive. To study osteocyte-specific and mechanically regulated DMP1 gene expression, the transcriptional activity of three cis-regulatory regions was first examined in an osteoblast differentiation model in vitro using a green fluorescent protein (GFP) reporter. Expression of the -9624 to +1996 bp (10 kb) and -7892 to +4439 bp (8 kb) DMP1 cis-regulatory regions dramatically increased in areas of mineralized matrix, in dendritic, osteocyte-like cells. Mineralizing cultures expressing the 8-kb construct show dramatic GFP increases in response to loading in cells with a dendritic morphology. Transgenic mice expressing the 8-kb DMP1-GFP and -2433 to +4439 bp (2.5 kb) DMP1-LacZ were generated. Osteocyte-specific expression was found with the 8 kb but not with the 2.5 kb in postnatal animals. However, the 2.5 kb could support expression in rapidly forming osteoblasts and pre-osteocytes in the embryo. Primary calvarial osteoblast cultures demonstrated that the 2.5 kb supports weak expression in a subset of osteoblasts and pre-osteocytes, but not in mature osteocytes. However, the 8 kb supports robust expression in primary bone marrow cultures. Therefore the region -7892 to -2433 bp, termed a 5.5-kb "Osteocyte Enhancer Module," appears to be required for osteocyte specificity. Ulnae of mice with the 8-kb DMP1-GFP were subjected to mechanical loading where GFP expression increased selectively and locally in osteocytes, distal to the mid-shaft and near the surface of the bone. Thus, the 8-kb region of the DMP1 gene is a target for mechano-transduction in osteocytes, and its cis-regulatory activity may be correlated to local strain in bone. [ABSTRACT FROM AUTHOR] more...
- Published
- 2005
- Full Text
- View/download PDF
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.