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Stabilization of HIF-1α alleviates osteoarthritis via enhancing mitophagy
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Stabilization of HIF-1α alleviates osteoarthritis via enhancing mitophagy
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Journal Article
Stabilization of HIF-1α alleviates osteoarthritis via enhancing mitophagy
2020
Overview
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.
Publisher
Nature Publishing Group UK,Springer Nature B.V
Subject
/ 38/61
/ 38/89
/ 42/44
/ 64/60
/ 96/1
/ 96/95
/ Amino Acids, Dicarboxylic - pharmacology
/ Animals
/ Biomedical and Life Sciences
/ Cartilage, Articular - metabolism
/ Cartilage, Articular - pathology
/ Cellular Senescence - drug effects
/ Cellular Senescence - genetics
/ Cytoprotection - drug effects
/ Extracellular Matrix - genetics
/ Extracellular Matrix - metabolism
/ Female
/ Humans
/ Hypoxia
/ Hypoxia-Inducible Factor 1, alpha Subunit - metabolism
/ Male
/ Protein Stability - drug effects
/ Reactive Oxygen Species - metabolism
/ siRNA
/ Surgery
