2022, Vol. 26 ›› Issue (20): 3133-3140

Mechanism of osteoarthritis induced chondrocyte apoptosis and extracellular matrix degradation

Wang Wei1, Tang Xiangyu2, Yi Zhiqian1, Liu Zhaoxu1   

Abstract: BACKGROUND: It has been found that long non-coding RNA (LncRNA) IFNG-AS1 plays a regulatory role in rheumatoid arthritis, but its role in osteoarthritis remains largely unknown.
OBJECTIVE: To investigate the effects of LncRNA IFNG-AS1 on proliferation, apoptosis and extracellular matrix degradation of chondrocytes in osteoarthritis via regulating miR-376b-3p/AKT serine/threonine kinase 3 (AKT3) axis.
METHODS: Real-time fluorescence quantitative PCR was used to detect the expression of IFNG-AS1, miR-376b-3p, and AKT3 in cartilage tissue of osteoarthritis and non-osteoarthritis patients. Cell proliferation, apoptosis, and the expression of extracellular matrix-related factors matrix metalloproteinase-3, matrix metalloproteinase-9 and matrix metalloproteinase-13 were analyzed by cell counting kit-8, flow cytometry and enzyme-linked immunosorbent assay. The interaction between miR-376b-3p and IFNG-AS1 or AKT3 was analyzed by dual luciferase reporter assay and RNA pull-down assay.
RESULTS AND CONCLUSION: Compared with normal cartilage tissue, the expression of IFNG-AS1 and AKT3 was increased in osteoarthritis cartilage tissue, while the expression of miR-376b-3p was decreased. Knockdown of IFNG-AS1 promoted cell proliferation but inhibited apoptosis and extracellular matrix degradation in chondrocytes. There was a targeted relationship between IFNG-AS1 and miR-376b-3p, and down-regulation of miR-376b-3p partially reversed the effect of IFNG-AS1 knockdown on chondrocytes (all P < 0.05). Further analysis showed that IFNG-AS1 that acted as ceRNA adsorbed miR-376b-3p and regulated the expression of AKT3, and up-regulation of AKT3 partially saved the effect of IFNG-AS1 knockdown on chondrocytes (all P < 0.05). To conclude, LncRNA IFNG-AS1 can inhibit chondrocyte proliferation but promote apoptosis and extracellular matrix degradation by regulating miR-376b-3p/AKT3 axis. IFNG-AS1 is expected to be a potential target for osteoarthritis therapy.
Key words: osteoarthritis, chondrocyte, long non-coding RNA IFNG-AS1, miR-376b-3p, AKT3