HIF-1α in Osteoarthritis: From Pathogenesis to Therapeutic Implications

Osteoarthritis is a common age-related joint degenerative disease. Pain, swelling, brief morning stiffness, and functional limitations are its main characteristics. There are still no well-established strategies to cure osteoarthritis. Therefore, better clarification of mechanisms associated with the onset and progression of osteoarthritis is critical to provide a theoretical basis for the establishment of novel preventive and therapeutic strategies. Chondrocytes exist in a hypoxic environment, and HIF-1 alpha plays a vital role in regulating hypoxic response. HIF-1 alpha responds to cellular oxygenation decreases in tissue regulating survival and growth arrest of chondrocytes. The activation of HIF-1 alpha could regulate autophagy and apoptosis of chondrocytes, decrease inflammatory cytokine synthesis, and regulate the chondrocyte extracellular matrix environment. Moreover, it could maintain the chondrogenic phenotype that regulates glycolysis and the mitochondrial function of osteoarthritis, resulting in a denser collagen matrix that delays cartilage degradation. Thus, HIF-1 alpha is likely to be a crucial therapeutic target for osteoarthritis via regulating chondrocyte inflammation and metabolism. In this review, we summarize the mechanism of hypoxia in the pathogenic mechanisms of osteoarthritis, and focus on a series of therapeutic treatments targeting HIF-1 alpha for osteoarthritis. Further clarification of the regulatory mechanisms of HIF-1 alpha in osteoarthritis may provide more useful clues to developing novel osteoarthritis treatment strategies.

Automated summary

Osteoarthritis is a common degenerative disease associated with age, for which there are currently no established cures. Understanding the mechanisms involved in the onset and progression of osteoarthritis is crucial for developing new preventive and therapeutic strategies. This review summarizes the role of hypoxia in the pathogenesis of osteoarthritis and focuses on therapeutic treatments targeting HIF-1 alpha. Further elucidation of the regulatory mechanisms of HIF-1 alpha in osteoarthritis may provide valuable insights for the development of novel osteoarthritis treatment strategies.