miRNAs have been reported to regulate cellular differentiation by modulating multiple signaling pathways. Long noncoding RNA (lnc RNA) DANCR was previously identified to be critical for the chondrogenesis of human synovium-derived mesenchymal stem cells (SMSC), however, the underlying molecular mechanism requires better understanding. Here, miRNA expression profiling in DANCR overexpressed in SMSCs identified significant down-regulation of miR-1305, which serves as a downstream target of DANCR. Notably, miR-1305 overexpression reversed DANCR-induced cell proliferation and chondrogenic differentiation of SMSCs, which suggested that miR-1305 antagonized the function of DANCR. Mechanistically, highly expressed miR-1305 resulted in the decreased expression of the TGF-β pathway member Smad4, and inhibition of miR-1305 enhanced the expression level of Smad4. Depletion of Smad4 suppressed the promotion of DANCR in cell proliferation and chondrogenesis of SMSCs. Collectively, our results characterized miR-1305-Smad4 axis as a major downstream functional mechanism of lncRNA DANCR in promoting the chondrogenesis in SMSCs.
Osteoarthritis (OA) is one of the most common chronic joint disease. Long non-coding RNAs (lncRNAs) have been confirmed to play important roles in a variety of diseases including OA. However, the underlying mechanism of lncRNA differentiation antagonizing non-protein coding RNA (DANCR) in OA has not been well elucidated. The expression of DANCR in cartilage tissues from OA patients was detected using quantitative real-time PCR. After cell transfection, the effects of DANCR inhibition on the proliferation, apoptosis and inflammatory factors of OA chondrocytes were detected using Cell Counting Kit-8 assay and flow cytometry assay. Novel target of DANCR was then identified through bioinformatics analysis and confirmed by luciferase reporter assay and RNA immunoprecipitation assay. The expression of DANCR was significantly increased in OA patients. Function assays demonstrated that DANCR suppression inhibited the proliferation, inflammation, and promoted apoptosis of chondrocytes cells. Additionally, DANCR regulated survival of OA chondrocytes through acting as a competitive endogenous RNA for miR-216a-5p. Furthermore, JAK2 was a direct target of miR-216a-5p, and DANCR regulated the JAK2/STAT3 signal pathway through miR-216a-5p in OA chondrocytes. In the present study, we concluded that DANCR promoted the proliferation, inflammation, and reduced cell apoptosis in OA chondrocytes through regulating miR-216a-5p/JAK2/STAT3 signaling pathway, indicating DANCR might be a useful biomarker and potential therapeutic target for OA treatment.
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