Abstract
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.
Highlights
Osteoarthritis (OA) is a leading cause of disabling disease worldwide[1]
Previous studies show that mitophagy induces chondrocytes degeneration, which indicated that Hypoxia inducible factor-1α (HIF-1α) is related to the OA development
We found that the HIF-1α protein expression levels were considerably elevated in the time-dependent manner and under hypoxia
Summary
Osteoarthritis (OA) is a leading cause of disabling disease worldwide[1]. It imposes a huge burden on the family affected, social welfare institutions and the social economic cost[2]. The incidence appears to be increased in the past decade. The incidence of osteoarthritis increased sharply in the elderly people[3]. Knee joint is the most common site of arthritis, followed by the hand and hip[4]. Pain is the most common clinical symptom of osteoarthritis[5]. When noninvasive and conservative treatment fails to achieve relieving symptom, surgery is the only last choice for patients[6]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
