Oxytocin Controls Chondrogenesis and Correlates with Osteoarthritis.

This study investigated the relationship of oxytocin (OT) to chondrogenesis and osteoarthritis (OA). Human bone marrow and multipotent adipose-derived stem cells were cultured in vitro in the absence or presence of OT and assayed for mRNA transcript expression along with histological and immunohistochemical analyses. To study the effects of OT in OA in vivo, a rat model and a human cohort of 63 men and 19 women with hand OA and healthy controls, respectively, were used. The baseline circulating OT, interleukin-6, leptin, and oestradiol levels were measured, and hand X-ray examinations were performed for each subject. OT induced increased aggrecan, collagen (Col) X, and cartilage oligomeric matrix protein mRNA transcript levels in vitro, and the immunolabelling experiments revealed a normalization of Sox9 and Col II protein expression levels. No histological differences in lesion severity were observed between rat OA groups. In the clinical study, a multivariate analysis adjusted for age, body mass index, and leptin levels revealed a significant association between OA and lower levels of OT (odds ratio = 0.77; p = 0.012). Serum OT levels are reduced in patients with hand OA, and OT showed a stimulatory effect on chondrogenesis. Thus, OT may contribute to the pathophysiology of OA.

Relationship of COL9A1 and SOX9 Genes with Genetic Susceptibility of Postmenopausal Osteoporosis.

As one of the most common types of osteoporosis, postmenopausal osteoporosis (PMOP) is caused by both genetic and environmental factors. Previous studies have indicated that SOX9 activity is tightly regulated to ensure normal bone mineral density (BMD) in the adult skeleton, and the COL9A1 promoter region can be transactivated by SOX9. In this study, we aimed to investigate the potential association between PMOP and the COL9A1 and SOX9 genes. A total of 10,443 postmenopausal women, including 2288 patients and 3557 controls in the discovery stage and 1566 patients and 3032 controls in the validation stage, were recruited. Forty-three tag SNPs (36 in COL9A1 and 7 in SOX9) were selected for genotyping to evaluate the association of the SOX9 gene with PMOP and BMD. Association and bioinformatics analyses were performed for PMOP. BMD and serum level of SOX9 were also utilized as quantitative phenotypes in further analyses. SNP rs73354570 of SOX9 was significantly associated with PMOP in both discovery stages (OR 1.24 [1.10-1.39], P = 3.56 × 10-4, χ2 = 12.75) and combined samples (OR 1.25 [1.15-1.37], P = 5.25 × 10-7, χ2 = 25.17). Further analyses showed that the SNP was also significantly associated with BMD and serum levels of the SOX9 protein. Our results provide further supportive evidence for the association of the SOX9 gene with PMOP and of the SOX9 gene with the variation of BMD in postmenopausal Han Chinese women. This study supports a role for SOX9 in the etiology of PMOP, adding to the current understanding of the susceptibility of osteoporosis.

Physical Activity Prevents Cartilage Degradation: A Metabolomics Study Pinpoints the Involvement of Vitamin B6.

Osteoarthritis (OA) is predominantly characterized by the progressive degradation of articular cartilage, the connective tissue produced by chondrocytes, due to an imbalance between anabolic and catabolic processes. In addition, physical activity (PA) is recognized as an important tool for counteracting OA. To evaluate PA effects on the chondrocyte lineage, we analyzed the expression of SOX9, COL2A1, and COMP in circulating progenitor cells following a half marathon (HM) performance. Therefore, we studied in-depth the involvement of metabolites affecting chondrocyte lineage, and we compared the metabolomic profile associated with PA by analyzing runners' sera before and after HM performance. Interestingly, this study highlighted that metabolites involved in vitamin B6 salvage, such as pyridoxal 5'-phosphate and pyridoxamine 5'-phosphate, were highly modulated. To evaluate the effects of vitamin B6 in cartilage cells, we treated differentiated mesenchymal stem cells and the SW1353 chondrosarcoma cell line with vitamin B6 in the presence of IL1ß, the inflammatory cytokine involved in OA. Our study describes, for the first time, the modulation of the vitamin B6 salvage pathway following PA and suggests a protective role of PA in OA through modulation of this pathway.

Decreased local and systematic matrix Gla protein (MGP) expression and its link to radiographic progression in ankylosing spondylitis patients.

BACKGROUND: Decreased serum levels of uncarboxylated matrix Gla-protein (ucMGP) have been detected in Ankylosing Spondylitis (AS) patients. The current study was to investigate the expression of MGP in AS tissues as well as the relationship between serum ucMGP (an inactive form of MGP) levels and radiographic severity in AS patients. METHODS: Local MGP expression were assessed by Western blot and RT-PCR in hip synovial tissues from patients with AS and control subjects. In addition, the serum level of ucMGP was assessed by enzyme-linked immunosorbent assay in 68 healthy subjects and 62 patients with AS. The radiographic progression of AS was classified according to the radiographic events of modified New York Criteria for sacroiliac joint evaluation and modified Stoke Ankylosing Spondylitis Spine Score (mSASSS) system for spine assessment. RESULTS: MGP expression was downregulated in AS patients compared to controls in hip tissues. Decreased levels of ucMGP in serum were found in AS patients compared with healthy controls. ucMGP levels in serum of AS patients were significantly negatively correlated with the disease radiographic severity evaluated by modified New York grading criteria (r = -0.293, p = 0.045) and mSASSS system (r = -0.361, p = 0.03). CONCLUSIONS: MGP expression is impaired in patients with AS. A low serum level of ucMGP in the setting of AS is linked to increased structural damage, emphasizing the role of MGP in the suppression of new bone formation.