The role of HIF-1α in hypoxic metabolic reprogramming in osteoarthritis

The joint dysfunction caused by osteoarthritis (OA) is increasingly becoming a major challenge in global healthcare, and there is currently no effective strategy to prevent the progression of OA. Therefore, better elucidating the relevant mechanisms of OA occurrence and development will provide theoretical basis for formulating new prevention and control strategies. Due to long-term exposure of cartilage tissue to the hypoxic microenvironment of joints, metabolic reprogramming changes occur. Hypoxia-inducible factor-1alpha (HIF-1α), as a core gene regulating hypoxia response in vivo, plays an important regulatory role in the hypoxic metabolism of chondrocytes. HIF-1α adapts to the hypoxic microenvironment by regulating metabolic reprogramming changes such as glycolysis, oxidative phosphorylation (OXPHOS), amino acid metabolism, and lipid metabolism in OA chondrocytes. In addition, HIF-1α also regulates macrophage polarization and synovial inflammation, chondrocytes degeneration and extracellular matrix (ECM) degradation, subchondral bone remodeling and angiogenesis in the hypoxic microenvironment of OA, and affects the pathophysiological progression of OA. Consequently, the regulation of chondrocytes metabolic reprogramming by HIF-1α has become an important therapeutic target for OA. Therefore, this article reviews the mechanism of hypoxia affecting chondrocyte metabolic reprogramming, focusing on the regulatory mechanism of HIF-1α on chondrocyte metabolic reprogramming, and summarizes potential effective ingredients or targets targeting chondrocyte metabolic reprogramming, in order to provide more beneficial basis for the prevention and treatment of clinical OA and the development of effective drugs.