Journal
CELL DEATH & DISEASE
Volume 11, Issue 6, Pages -Publisher
SPRINGERNATURE
DOI: 10.1038/s41419-020-2680-0
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Funding
- National Nature Foundation of China [81722028, 81871806, 81972150]
- Zhejiang Public Service Technology Research Program/Social Development [LGF18H060008]
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Mitochondrial dysfunction leads to osteoarthritis (OA) and disc degeneration. Hypoxia inducible factor-1 alpha (HIF-1 alpha) mediated mitophagy has a protective role in several diseases. However, the underlying mechanism of HIF-1 alpha mediated mitophagy in OA remains largely unknown. This current study was performed to determine the effect of HIF-1 alpha 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 alpha was increased in human and mouse OA cartilage. HIF-1 alpha knockdown by siRNA further impair the hypoxia-induced mitochondrial dysfunction; In contrast, HIF-1 alpha mediated protective role was reinforced by prolylhydroxylase (PHD) inhibitor dimethyloxalylglycine (DMOG). In addition, HIF-1 alpha 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 alpha mediated mitophagy could alleviate OA, which may serve as a promising strategy for OA treatment.
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