Osteoarthritis (OA) is an age-related chronic progressive degenerative disease that induces persistent pain and disabilities. The development of OA is a complex process, and the risk factors are various, including aging, genetics, trauma and altered biomechanics. Inflammation and immunity play an important role in the pathogenesis of OA. JAK/STAT pathway is one of the most prominent intracellular signaling pathways, regulating cell proliferation, differentiation, and apoptosis. Inflammatory factors can act as the initiators of JAK/STAT pathway, which is implicated in the pathophysiological activity of chondrocyte. In this article, we provide a review on the importance of JAK/STAT pathway in the pathological development of OA. Potentially, JAK/STAT pathway becomes a therapeutic target for managing OA.

Abnormal mechanical stimulation contributes to articular cartilage degeneration and osteoarthritis (OA) development. Many long noncoding RNAs (lncRNAs) are involved in mechanical force-induced cartilage degeneration. LncRNA HOTAIR (HOTAIR) has been demonstrated to increase osteoarthritis progression. However, the roles of HOTAIR in mechanical stimulation-treated chondrocytes are still unclear. In this study, we found that mechanical stimulation significantly induced apoptosis in C28/I2 cells. In addition, the expression of HOTAIR was up regulated and the expression of miR-221 was down regulated. Knockdown of HOTAIR effectively ameliorated cell apoptosis induced by mechanical stimulation. HOTAIR could interact with miR-221, which targeted to degrade BBC3. Overexpression of BBC3 could reverse the decreased apoptotic rates induced by HOTAIR knockdown. Collectively, HOTAIR promoted mechanical stimulation-induced apoptosis by regulating the miR-221/BBC3 axis in C28/I2 cells.

Osteoarthritis (OA) is the most frequent and disabling disease in developed countries. The progressive degeneration of articular cartilage characterized as thinner and erosive. Inflammation is well-known to be involved in OA development. However, there are no effective therapeutic strategies to cure it. Xanthohumol (XH) is a natural prenylflavonoid isolated from hops and beer. The protective activity of XH against OA chondrocytes inflammation and ECM degradation is unclear. In this article, we found that XH significantly inhibited inflammatory responses, attenuated catabolic enzymes expression, and ameliorated ECM degradation, as showed by decreased production of NO, PGE2, TNFα, and IL-6, decreased expression of MMP-3/-13 and ADAMTS-4/-5, and increased expression of collagen-II and aggrecan. In addition, XH activated HO-1 signaling and attenuated IL-1β-induced C/EBPβ. XH promoted the interaction between HO-1 and C/EBPβ, inhibiting the nuclear translocation of C/EBPβ. HO-1 knockdown could abrogate the protective effects of XH in IL-1β-treated chondrocytes. Collectively, XH attenuated inflammatory responses and ECM degradation by mediating HO-1 and C/EBPβ signaling pathways in osteoarthritis chondrocytes.

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Osteoporosis, characterized by decreased mineral density and bone mass, is triggered by various detrimental factors and often causes further complications, including fractures. Aberrant expression of microRNAs (miRs) has been associated with the pathogenesis of osteoporosis. Recently, miR-142 was reported to be downregulated in osteoblasts; however, the underlying mechanism of miR-142 in mediating the development of osteoporosis remains unclear. In the present study, high glucose induced the downregulation of miR-142 mRNA expression and promoted the apoptosis of MC3T3-E1 cells. miR-142-mimics significantly protected against high glucose-induced apoptosis, upregulated the expression levels of B-cell lymphoma 2 (Bcl-2) and downregulated the protein expression levels of β-catenin, Bcl-2 associated X (Bax) and caspase-3. Furthermore, β-catenin was identified as a direct target of miR-142 using luciferase reporter assays. Similar to the effects of miR-142 inhibitors, overexpression of β-catenin aggravated the apoptosis of MC3T3-E1 cells, as demonstrated by the upregulation of Bax and caspase-3, and the downregulation of Bcl-2 expression levels. In conclusion, miR-142 protects MC3T3-E1 cells against high glucose-induced apoptosis by targeting β-catenin.