Stabilization of HIF-1? alleviates osteoarthritis via enhancing mitophagy.

ABSTRACT: Mitochondrial dysfunction leads to osteoarthritis (OA) and disc degeneration. Hypoxia inducible factor-1? (HIF-1?) mediated mitophagy has a protective role in several diseases. However, the underlying mechanism of HIF-1? mediated mitophagy in OA remains largely unknown. This current study was performed to determine the effect of HIF-1? 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-1? was increased in human and mouse OA cartilage. HIF-1? knockdown by siRNA further impair the hypoxia-induced mitochondrial dysfunction; In contrast, HIF-1? mediated protective role was reinforced by prolylhydroxylase (PHD) inhibitor dimethyloxalylglycine (DMOG). In addition, HIF-1? 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-1? mediated mitophagy could alleviate OA, which may serve as a promising strategy for OA treatment.

SUBMITTER: Hu S 

PROVIDER: S-EPMC7316774 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature