Effects of GLA on IL-1β-Induced Autophagy and Apoptosis in Articular Chondrocytes via PINK1/Parkin Pathway
Objective:To investigate the effect of geniposide(GLA)on PTEN-induced kinase 1(PINK1)/E3 ubiquitin ligase(Parkin)signaling pathway in regulating autophagy and apoptosis of articular chondrocytes induced by interleukin-1β(IL-1β).Methods:Articular chondrocytes were divided into Con-trol,IL-1β,Low-GLA,Medium-GLA,High-GLA,and Suramin groups.Cell proliferation was assessed u-sing the Cell Counting Kit-8(CCK8)assay.Autophagy was detected by transmission electron microscopy(TEM).Apoptosis was measured by flow cytometry.Levels of inflammatory factors(MMP3,TNF-α,MMP13)and reactive oxygen species(ROS)in chondrocytes were detected by ELISA.Protein expressions of cleaved caspase-3,microtubule-associated protein 1 light chain 3(LC3)I,LC3Ⅱ,P62,PINK1,and Par-kin were analyzed by Western blot.Results:Compared with the Control group,the IL-1β group showed de-creased cell viability,LC3Ⅱ/Ⅰ ratio,PINK1,and Parkin,while autophagic vacuole number,apoptosis rate,MMP3,TNF-α,MMP13,ROS,cleaved caspase-3,and P62 were increased(P＜0.05).The Low-GLA,Medium-GLA,and High-GLA groups exhibited higher cell viability,autophagic vacuole number,LC3Ⅱ/Ⅰ ratio,PINK1,and Parkin than the IL-1β group,with lower apoptosis rate,MMP3,TNF-α,MMP13,ROS,cleaved caspase-3,and P62(P＜0.05).The Suramin group showed lower cell viability,autophagic vacuole number,LC3Ⅱ/Ⅰ ratio,PINK1,and Parkin than the High-GLA group,with higher apoptosis rate,MMP3,TNF-α,MMP13,ROS,cleaved caspase-3,and P62(P＜0.05).Conclusion:GLA inhibits the progression of osteoarthritis(OA)by activating autophagy and inhibiting apoptosis in IL-1β-induced articular chondro-cytes,possibly through the activation of the PINK1/Parkin signaling pathway.
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