Mitochondrial dysfunction leads to osteoarthritis (OA) and disc degeneration. Hypoxia inducible factor-1α (HIF-1α) mediated mitophagy has a protective role in several diseases. However, the underlying mechanism of HIF-1α mediated mitophagy in OA remains largely unknown. This current study was performed to determine the effect of HIF-1α mediated mitophagy on OA. Therefore, X-ray and tissue staining including HE staining, safranin O-fast green (S-O) and Alcian Blue were used to assess imageology and histomorphology differences of mouse knee joint. Transcriptional analysis was used to find the possible targets in osteoarthritis. Western blot analysis, RT-qPCR and immunofluorescence staining were used to detect the changes in gene and protein levels in the vitro experiment. The expression of HIF-1α was increased in human and mouse OA cartilage. HIF-1α knockdown by siRNA further impair the hypoxia-induced mitochondrial dysfunction; In contrast, HIF-1α mediated protective role was reinforced by prolylhydroxylase (PHD) inhibitor dimethyloxalylglycine (DMOG). In addition, HIF-1α stabilization could alleviate apoptosis and senescence via mitophagy in chondrocytes under hypoxia condition, which could also ameliorate surgery-induced cartilage degradation in mice OA model. In conclusion, HIF-1α mediated mitophagy could alleviate OA, which may serve as a promising strategy for OA treatment.

线粒体功能障碍导致骨关节炎（OA）和椎间盘退变。低氧诱导因子-1α（HIF-1α）介导的线粒体吞噬对几种疾病具有保护作用。但是，在OA中HIF-1α介导的线粒体吞噬的基本机制仍然未知。进行这项当前的研究以确定HIF-1α介导的线粒体对OA的影响。因此，使用X射线和组织染色，包括HE染色，番红蛋白O型坚牢绿色（SO）和Alcian Blue来评估小鼠膝关节的影像学和组织形态学差异。转录分析用于发现骨关节炎的可能目标。在体外实验中，使用蛋白质印迹分析，RT-qPCR和免疫荧光染色检测基因和蛋白质水平的变化。HIF-1α在人和小鼠OA软骨中表达增加。siRNA敲低HIF-1α进一步削弱了低氧引起的线粒体功能障碍。相反，脯氨酰羟化酶（PHD）抑制剂二甲基草酰甘氨酸（DMOG）增强了HIF-1α介导的保护作用。此外，在缺氧条件下，HIF-1α的稳定可以通过线粒体吞噬减轻软骨细胞的凋亡和衰老，也可以减轻小鼠OA模型中由于手术引起的软骨退化。总之，HIF-1α介导的线粒体吞噬可以减轻OA，这可能是有希望的OA治疗策略。HIF-1α的稳定可以通过缺氧条件下软骨细胞的线粒体吞噬减轻细胞凋亡和衰老，也可以减轻小鼠OA模型中由于手术引起的软骨降解。总之，HIF-1α介导的线粒体吞噬可以减轻OA，这可能是有希望的OA治疗策略。HIF-1α的稳定可以通过缺氧条件下软骨细胞的线粒体吞噬减轻细胞凋亡和衰老，也可以减轻小鼠OA模型中由于手术引起的软骨降解。总之，HIF-1α介导的线粒体吞噬可以减轻OA，这可能是有希望的OA治疗策略。