LncRNA MEG3 Inhibits the Degradation of the Extracellular Matrix of Chondrocytes in Osteoarthritis via Targeting miR-93/TGFBR2 Axis

Background As a degenerative joint disease, osteoarthritis (OA) is characterized by articular cartilage degradation. Long noncoding RNAs (lncRNAs) act critical roles in the regulation of OA development, including affecting the proliferation, apoptosis, extracellular matrix (ECM) degradation, and inflammatory response of chondrocytes. The current study's aim was to investigate the regulatory function and the underlying molecular mechanism of lncRNA MEG3 in ECM degradation of chondrocytes in OA. Methods In the current study, chondrocytes were induced by interleukin-1 beta (IL-1 beta) to simulate OA condition, and further assessed cell viability, lncRNA MEG3 and miR-93 expression levels. Overexpression or knockdown of lncRNA MEG3 in chondrocytes treated with IL-1 beta were performed to investigate the function of MEG3 in regulating cell proliferation, apoptosis and ECM degradation using EdU assay, flow cytometry, quantitative reverse transcription polymerase chain reaction (qRT-PCR), and Western blot. The interaction between MEG3 and miR-93 was assessed using qRT-PCR. Furthermore, overexpression of miR-93 was performed as recovery experiment to explore the functional mechanism of MEG3. Results MEG3 was significantly downregulated in chondrocytes treated with IL-1 beta, whereas miR-93 was upregulated concomitantly. Overexpression of MEG3 induced the proliferation, suppressed the apoptosis, and relieved the degradation of ECM in IL-1 beta-induced chondrocytes. By contrast, knockdown of MEG3 suppressed the proliferation, promoted the apoptosis, and aggravated ECM degradation in IL-1 beta induced chondrocytes. In addition, MEG3 was found to relieve the inhibitive expression of TGFBR2 as a competitive endogenous RNA (ceRNA) of miR-93, and then activated transforming growth factor-beta (TGF-beta) signaling pathway, regulated chondrocytes ECM degradation in IL-1 beta induced chondrocytes subsequently. Conclusion LncRNA MEG3 targeted miR-93/TGFBR2 axis, regulated the proliferation, apoptosis and ECM degradation of chondrocytes in OA.

Automated summary

The study revealed that MEG3 was significantly downregulated and miR-93 was upregulated in chondrocytes treated with IL-1 beta. Overexpression of MEG3 promoted cell proliferation, inhibited apoptosis, and relieved ECM degradation, while knockdown of MEG3 had the opposite effects. MEG3 was found to act as a ceRNA of miR-93 to relieve the inhibitive expression of TGFBR2 and activate the TGF-beta signaling pathway, thus regulating chondrocytes ECM degradation.