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Mechanical-stress has been reported to trigger cartilage fibrosis, in which transforming growth factor (TGF)-β and connective tissue growth factor (CCN2) are involved. However, the function of integrin-α5β1, a cytomembrane receptor, on mechanical-stress related fibrosis has not yet been elucidated. This study aims to reveal the interaction of TGF-β1/CCN2/integrin-α5β1 in the mechanical-stress induced chondrocyte (CH) fibrosis. We used different levels (5% and 10%) of cyclic tension simulation (CTS) to stretch CHs and observed the gene expression of TGF-β1/CCN2/integrin-α5β1 as well as the fibrous related genes containing collagen I/II/III, Runx2, MMP13, and ADAMTS-5 by real-time polymerase chain reaction (RT-PCR) or immunofluorescence. We used the siRNA or the corresponding antagonist of TGF-β1, CCN2, integrin-α5β1 during the CTS to clear the effect of them in the fibrosis progress. In addition, to verify the crosstalk between TGF-β1, CCN2, and integrin-α5β1, we used the recombinant human (rh)-TGF-β1 and expression can alleviate the fibrous process. To clarify the biological function of miRNA-128-3p in influencing the progression of osteoporosis by inducing osteogenic differentiation of MSCs via activating the Wnt3a signaling. Dynamic expression levels of miRNA-128-3p in osteogenically differentiated MSCs at the different time points were detected by qRT-PCR. The binding sites in the seed sequence of miRNA-128-3p and Wnt3a were predicted using the bioinformatic tool, and their interaction was further confirmed by Dual-Luciferase reporter assay. Co-regulation of miRNA-128-3p and Wnt3a on relative levels of osteogenesis-associated genes, ALP activity and mineralization ability in glucocorticoid-induced MSCs were assessed. MiRNA-128-3p was gradually upregulated with the prolongation of osteogenic differentiation of MSCs. Overexpression of miRNA-128-3p reversed the declines in glucocorticoid-induced expression levels of osteogenesis-associated genes (Bglap, RUNX2 and BMP-2), ALP activity and mineralization ability in MSCs. Wnt3a was able to bind miRNA-128-3p. Its level was positively regulated by miRNA-128-3p in MSCs. Enhanced ALP activity and mineralization ability in glucocorticoid-induced MSCs overexpressing Wnt3a were partially abolished by knockdown of miRNA-128-3p. By positively regulating Wnt3a, miRNA-128-3p alleviates the progression of osteoporosis through inducing osteogenic differentiation of MSCs. By positively regulating Wnt3a, miRNA-128-3p alleviates the progression of osteoporosis through inducing osteogenic differentiation of MSCs. Osteoarthritis (OA) is a prevalent chronic orthopedic disease, but its relationship with the lncRNA OIP5 Antisense RNA 1(OIP5-AS1)/micro-30a-5p axis is still under investigation. This study was designed to explore the regulatory function of this axis on chondrocytes. A quantitative polymerase chain reaction (qPCR) assay was carried out to quantify lncRNA OIP5-AS1 and micro-30a-5p in cartilage tissues of patients with OA, and lncRNA OIP5-AS1 siRNA, micro-30a-5p mimics, and micro-30a-5p inhibitor vectors were constructed to analyze the functions of lncRNA OIP5-AS1/micro-30a-5p on chondrocytes. In addition, the Western blot was used to determine the levels of proteins in chondrocytes, the 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT)assay to determine the viability of chondrocytes, the flow cytometry to analyze apoptosis and cycle of them, and the Dual-Luciferase reporter gene assay to verify the targeting relationship between LncRNA OIP5-AS1 and micro-30a-5p. LncRNA OIP5-AS1 in cartilcro-30a-5p is beneficial to patients with OA. HIF-1α and Runx2 expression usually increase in chondrocytes (CHs) during osteoarthritis (OA), which involves the changes in glycolytic metabolism. However, the molecular regulation of HIF-1α related to the CHs glycolytic metabolism is still unclear. In this study, we aimed to reveal the mediation of HIF-1α by Runx2 and its effect on the glycolytic metabolism of degenerative CHs. The expression of HIF-1α, Runx2, and the degenerative markers of CHs in both natural conditions from the OA patients and IL-1β treated in vitro model was analyzed by a Western blot or real-time polymerase chain reaction (RT-PCR). The glycolytic metabolism was determined by the intracellular glucose uptake and adenosine triphosphate (ATP) generation. Transfection of siRNA coding HIF-1α or Runx2 was used to clear the function between HIF-1α and Runx2 in the glycolytic metabolism of degenerated CHs caused by IL-1β. Chromatin immunoprecipitation (ChIP) and Luciferase reporter gene assay were used to verify the Runx2 protein binds to the promoter of HIF-1α and promote its expression. HIF-1α and Runx2 were increased, and glucose uptake and ATP generation were decreased in the degenerative CHs from both OA and IL-1β conditions. Under the stimulation of IL-1β, Runx2 silencing rejected the upregulation of HIF-1α and further aggravated the glycolytic metabolism. When HIF-1α was silenced, the glycolytic metabolism of CHs was also suppressed. Besides, Runx2 protein could regulate HIF-1α expression in the transcriptional level by binding to its promoter. OHIF-1α plays a role in the self-repair of the glycolytic metabolism of degenerative CHs via the transcriptional regulation of Runx2. OHIF-1α plays a role in the self-repair of the glycolytic metabolism of degenerative CHs via the transcriptional regulation of Runx2.Although obesity is known to have an influence on fracture, the relationship between lumbar and femur fractures and weight or waist circumference is controversial. We investigated the incidence of fracture with regards to waist circumference using the customised database of the Korean National Health Insurance Service (NHIS). Among 8,922,940 adults who participated at least twice in the NHIS National Health Check-up Program in South Korea between 2009 and 2011, 1,556,751 subjects (780,074 men and 776,677 women) were extracted. Over a mean follow-up of 6.5 years, multivariate-adjusted logistic regression analysis demonstrated that higher waist circumference was associated with an increased risk of femur fractures in both males and females. https://www.selleckchem.com/products/hydroxychloroquine-sulfate.html Moreover, the incidence of lumbar fractures was also positively associated with an increased waist circumference in males and females. An increased waist circumference showed a positive linear relationship with the risk of lumbar and femur fractures in both males and females.
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