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Known to be involved in bone‐cartilage metabolism, Vitamin D (VD) may play a role in human's disc pathophysiology. Given that postmenopausal women are prone to suffer VD deficiency and intervertebral disc degeneration (IDD), this study is intended to investigate whether VD can delay IDD in ovariectomized rats by improving bone microstructure and antioxidant stress. Female Sprague–Dawley rats were randomly allocated into four groups: sham, oophorectomy (OVX)+VD deficiency (VDD), OVX, and OVX+VD supplementation (VDS). In vivo, after a 6‐month intervention, imaging and pathology slice examinations showed that IDD induced by OVX was significantly alleviated in VDS and deteriorated by VDD. The expressions of aggrecan and Collagen II in intervertebral disc were reduced by OVX and VDD, and elevated by VDS. Compared with the OVX+VDD and OVX group vertebrae, OVX+VDS group vertebrae showed significantly improved endplate porosity and lumbar bone mineral density with increased percent bone volume and trabecular thickness. Furthermore, 1α,25(OH)2D3 restored the redox balance (total antioxidant capacity, ratio of oxidized glutathione/glutathione) in the disc. The cocultivation of 1α,25(OH)2D3 and nucleus pulposus cells (NPCs) was conducted to observe its potential ability to resist excessive oxidative stress damage induced by H2O2. In vitro experiments revealed that 1α,25(OH)2D3 reduced the senescence, apoptosis, and extracellular matrix degradation induced by H2O2 in NPCs. In conclusion, VDS exhibits protective effects in OVX‐induced IDD, partly by regulating the redox balance and preserving the microstructure of endplate. This finding provides a new idea for the prevention and treatment of IDD. [ABSTRACT FROM AUTHOR]

Intervertebral disk degeneration (IVDD) is the major cause of low back pain. Alpha-ketoglutaric acid (α-KG), an important intermediate in energy metabolism, has various functions, including epigenetic regulation, maintenance of redox homeostasis, and antiaging, but whether it can ameliorate IVDD has not been reported. Here, we examined the impacts of long-term administration of α-KG on aging-associated IVDD in adult rats. In vivo and in vitro experiments showed that α-KG supplementation effectively ameliorated IVDD in rats and the senescence of nucleus pulposus cells (NPCs). α-KG supplementation significantly attenuated senescence, apoptosis, and matrix metalloproteinase-13 (MMP-13) protein expression, and it increased the synthesis of aggrecan and collagen II in IL-1β-treated NPCs. In addition, α-KG supplementation reduced the levels of IL-6, phosphorylated JAK2 and STAT3, and the nuclear translocation of p-STAT3 in IL-1β-induced degenerating NPCs. The effects of α-KG were enhanced by AG490 in NPCs. The underlying mechanism may involve the inhibition of JAK2/STAT3 phosphorylation and the reduction of IL-6 expression. Our findings may help in the development of new therapeutic strategies for IVDD.NEW & NOTEWORTHY Alpha-ketoglutaric acid (α-KG) exerted its protective effect on nucleus pulposus cells' (NPCs) degeneration by inhibiting the senescence-associated secretory phenotype and extracellular matrix degradation. The possible mechanism may be associated with negatively regulating the JAK2/STAT3 phosphorylation and the decreased IL-6 expression, which could be explained by a blockage of the positive feedback control loop between IL-6 and JAK2/STAT3 pathway. [ABSTRACT FROM AUTHOR]

Background: The relationship between a poor nutritional state and the risk of fractures has not been investigated. This study aimed to investigate the ability of the Controlling Nutritional Status (CONUT) and Geriatric Nutritional Risk Index (GNRI) to predict the incidence of subsequent vertebral fracture (SVF) after percutaneous vertebroplasty (PVP). Methods: A total of 307 women and 138 men over 50 years old who underwent PVP for osteoporotic vertebral compression fracture (OVCF) were included. Blood biochemical indexes, body mass index (BMI), bone mineral density (BMD), physical function, and muscle strength were measured at baseline. Cox regression analysis was used to determine whether nutritional state was an independent predictor for SVF. Results: During follow-up, 35 (25.4%) men and 85 (27.7%) women suffered SVF. Patients with SVF had lower BMI, serum albumin levels, GNRI scores, grip strength, lumbar BMD, and Short-Physical Performance Battery (SPPB) scores and higher fall rates and CONUT scores (P < 0.05). Compared with normal nutrition, mild malnutrition was associated with higher risk for SVF (women: HR 2.37, p=0.001, men: HR 2.97, p=0.021 by GNRI; women: HR 2.36, p=0.005, men: HR 3.62, p=0.002 by CONUT) after adjusting for confounding factors. Those with moderate–severe malnutrition also had a higher risk of SVF. Kaplan–Meier analysis showed that poor nutrition state was significantly associated with lower SVF-free survival (P< 0.05). The area under curve (AUC) for predicting SVF was 0.65 and 0.73 for the GNRI and 0.67 and 0.66 for the CONUT in men and women, respectively. Conclusion: GNRI and CONUT are simple and effective tools for predicting SVF in patients undergoing PVP. Health management and nutrition supplement after PVP is a potentially effective prevention strategy against SVF. [ABSTRACT FROM AUTHOR]

Pulmonary fibrosis (PF) is a severe chronic lung disease with little effective treatment options other than lung transplantation. Adipose-derived mesenchymal stem cells (ADSCs) have been shown to exert therapeutic effects on PF, but the underlying mechanisms remain to be further elucidated. Here, we show the interaction of ADSCs and lung-originated cells at the single-cell level, using bleomycin- (BLM-) induced mice PF model and green fluorescent protein– (GFP–) labeled mouse ADSCs. The intratracheally injected ADSCs were successfully recollected with flow cytometry and, together with lung-originated cells, were subjected to single-cell RNA sequencing (scRNA-seq). The ADSC treatment drastically changed the transcriptomic profile and composition of lung cells, especially macrophages. We explored the signal pathway interactions between ADSCs and lung-originated cells, showing potentially regulative pathways including NGR, ANNEXIN, HGF, and PERIOSTIN. Our data indicate that the injected ADSCs increased the number of Trem2+ antiinflammatory lung macrophages and lowered further inflammation and fibrosis in the lung. Our work realized the direct analysis of injected ADSCs to explore its in vivo interaction with the lung environment under PF and may provide critical information for future engineering of ADSCs to achieve better therapeutic effects in PF. [ABSTRACT FROM AUTHOR]

Background: Postoperative sacroiliac joint pain (SIJP) is a common manifestation of failed back surgery syndrome after a posterior lumbar interbody fusion (PLIF). However, there is currently no consensus on the risk factors for SIJP after PLIF., Objectives: We explored the effects of abdominal obesity and sagittal imbalance on SIJP after PLIF., Study Design: This is a prospective observational cohort study., Setting: This study occurred at the Department of Spinal Surgery at a hospital affiliated with a medical university., Methods: A total of 401 patients who underwent PLIF from June 2018 to June 2021 were enrolled in this study. 36 patients experienced postoperative SIJP. In contrast, a matched group comprised 72 non-SIJP patients. We used 1:2 propensity score matching to compare obesity features and sagittal spine parameters in the 2 groups. Inflammatory cytokines and visual analog scale (VAS) scores were measured in the SIJP group., Results: A total of 36 patients (8.98%) experienced SIJP during the follow-up. Compared with the non-SIJP group, patients with postoperative SIJP had a higher body mass index (BMI), greater abdominal obesity, a higher incidence of pelvic incidence-lumbar lordosis greater than 10°, and a higher incidence of a sagittal vertical axis greater than 5 cm (P < 0.05). Receiver operating characteristic curve analysis showed that the area under the curve for waist circumference was greater than that for BMI (0.762 vs. 0.650, P = 0.049). Logistic regression analysis revealed that the risk factors for SIJP were abdominal obesity, a pelvic incidence-lumbar lordosis of greater than 10°, and a sagittal vertical axis greater than 5 cm (P < 0.05). In patients with SIJP, interleukin 6, tumor necrosis factor-α, and VAS scores were higher in the abdominal obesity group than in the non-abdominal obesity group (P < 0.05)., Limitations: There was no uniform diagnosis of SIJP, so the incidence rate of SIJP might not be accurate., Conclusions: The significant predictors of SIJP were abdominal obesity and sagittal imbalance. Patients with abdominal obesity showed higher levels of inflammatory markers and pain intensity. More attention should be paid to body shape and the angle of correction of lumbar lordosis before lumbar surgery.

Background: Intervertebral disc degeneration (IVDD), which contributes to stenosis of the spinal segment, commonly causes lower back pain. The process of IVDD degradation entails gradual structural adjustments accompanied by extreme transformations in metabolic homeostasis. However, the molecular and cellular mechanisms associated with IVDD are poorly understood. Methods: The RNA-sequencing datasets GSE34095 and GSE56081 were obtained from the Gene Expression Omnibus (GEO) database. Ferroptosis-related differentially expressed genes (DEGs) were identified from these gene sets. The protein-protein interaction (PPI) network was established and visualized using the STRING database and Cytoscape software, and the key functional modules of ferroptosis-related genes were identified. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed on the DEGs. Weighted gene co-expression network analysis (WGCNA), immune infiltration analysis in the GEO database, and other GSE series were used as validation datasets. The xCELL algorithm was performed to investigate the immune cell infiltration differences between the degenerated IVDD and control groups. Results: The major genes involved in nucleus pulposus tissue immune infiltration and ferroptosis-related genes were mined by bioinformatics analysis. A total of 3,056 DEGs were obtained between the IVDD tissue and control groups. The DEGs were enriched in the cell cycle; apoptosis; necroptosis; and the PI3K-Akt, Hippo, and HIF-1 signaling pathways. PCR and Western blot techniques were utilized to confirm the differential ferroptosis-related genes. The results indicated that the protein expression levels of NCOA4 and PCBP1 were elevated, while the protein expression level of GPX4 was reduced in NPCs following IL-1β treatment. Our study has found that severe disc tissue degeneration leads to a noteworthy increase in the expression of CD8A in naive T cells, CCR7 in memory CD4 + cells, GZMB in natural killer (NK) cells, and CD163 and CD45 in macrophages. Conclusion: Our data demonstrate that ferroptosis occurs in IVDD, suggesting that ferroptosis may also increase IVDD improvement by triggering immune infiltration. This work was conducted to further understand IVDD pathogenesis and identify new treatment strategies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Liu, Xu, Yi, Zhang and Wang.)

Background: Obesity had been previously considered to be a protective factor against osteoporosis or fractures; however, recent research indicates that obesity, especially abdominal obesity, may increase the risk of some types of fractures., Objective: We explored the effects of abdominal obesity on subsequent vertebral fracture (SVF) after percutaneous vertebral augmentation (PVA)., Study Design: A prospective observational cohort study., Setting: Department of Spinal Surgery of a hospital affiliated with a medical university., Methods: A total of 390 women and 237 men aged > 50 years suffering from osteoporotic vertebral fracture (OVF) were included. Weight, height, bone mineral density (BMD), abdominal circumference, and other basic information were measured at baseline and 1-year follow-up visit., Results: During follow-up, 80 (33.7%) men and 143 (36.7%) women incurred SVF. Greater waist circumference (WC) and waist-to-hip ratio (WHR) increased the risk of SVF in men (WC: HR 1.83, P = 0.016; WHR: HR 1.63, P = 0.045) and women (WC: HR 2.75, P = 0.001; WHR: HR 2.63, P = 0.001) after adjustment for BMD and other potential confounders. Compared with normal BMI, being overweight was associated with lower SVF risk (women: HR 0.55, P = 0.044; men: HR 0.46, P = 0.046), and obesity was associated with greater SVF risk (women: HR 4.53, P < 0.001; men: HR 3.77, P < 0.001) in both genders. We observed a nonlinear relationship between BMI and SVF with a U-shaped curve; after adjusting BMD, this became a reverse J-curve., Limitations: There was no further statistical analysis of the relationship between abdominal obesity and other fracture sites. Asymptomatic SVF may underestimate the impact of abdominal obesity on the occurrence of SVF., Conclusions: Abdominal obesity was significantly associated with a higher risk of SVF after PVA. Management of body type after PVA may be an effective prevention strategy against SVF.