Abstract
Chondrocyte production of catabolic and inflammatory mediators participating in extracellular matrix degradation has been regarded as a central event in osteoarthritis (OA) development. During OA pathogenesis, interleukin-1β (IL-1β) decreases the mRNA expression and protein levels of transforming growth factor-β receptor type-2 (TGFBR2), thus disrupting transforming growth factor-β signaling and promoting OA development. In the present study, we attempted to identify the differentially expressed genes in OA chondrocytes upon IL-1β treatment, investigate their specific roles in OA development, and reveal the underlying mechanism. As shown by online data analysis and experimental results, TGFBR2 expression was significantly downregulated in IL-1β-treated human primary OA chondrocytes. IL-1β treatment induced degenerative changes in OA chondrocytes, as manifested by increased matrix metalloproteinase 13 and a disintegrin and metalloproteinase with thrombospondin motifs 5 proteins, decreased Aggrecan and Collagen II proteins, and suppressed OA chondrocyte proliferation. These degenerative changes were significantly reversed by TGFBR2 overexpression. miR-302c expression was markedly induced by IL-1β treatment in OA chondrocytes. miR-302c suppressed the expression of TGFBR2 via direct binding to its 3′- untranslated region. Similar to TGFBR2 overexpression, miR-302c inhibition significantly improved IL-1β-induced degenerative changes in OA chondrocytes. Conversely, TGFBR2 silencing enhanced IL-1β-induced degenerative changes and significantly reversed the effects of miR-302c inhibition in response to IL-1β treatment. In conclusion, the miR-302c/TGFBR2 axis could modulate IL-1β-induced degenerative changes in OA chondrocytes and might become a novel target for OA treatment.
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This study was supported by Natural Science Foundation of Hunan Province [Grant No. 2018JJ3725].
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All procedures performed in studies involving human participants were in accordance with the Ethics Committee of the Second Xiangya Hospital and with the 1964 Helsinki declaration. All the participants have signed the informed consents.
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Chen, Y., Chen, Y., Wang, W. et al. The miR-302c/transforming growth factor-β receptor type-2 axis modulates interleukin-1β-induced degenerative changes in osteoarthritic chondrocytes. J. Cell Commun. Signal. 16, 93–102 (2022). https://doi.org/10.1007/s12079-020-00591-2
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DOI: https://doi.org/10.1007/s12079-020-00591-2