Hypoxia and osteoarthritis: how chondrocytes survive hypoxic environments

PURPOSE OF REVIEW: This review summarizes the current knowledge about hypoxia and hypoxia-inducible factor-1 (HIF-1) for chondrocyte survival, energy generation and matrix synthesis of articular chondrocytes during cartilage homeostasis and disease. RECENT FINDINGS: In recent years increasing evidence of a pivotal role of hypoxia and the transcription factor HIF-1alpha in cartilaginous tissues has been published. Growth plates with functionally inactivated hypoxia-inducible factor-1alpha display great defects in their central areas caused by massive cell death. This very important observation indicates that hypoxia-inducible factor-1alpha is absolutely necessary for chondrocytes to survive extremely low oxygen tensions. Furthermore, hypoxia-inducible factor-1alpha has been shown to have very important functions for the regulation of glucose transport, anaerobic energy generation and matrix synthesis by articular chondrocytes. Besides hypoxia, other factors such as proinflammatory mediators and mechanical load have been shown to increase hypoxia-inducible factor-1alpha activity in articular chondrocytes. All these factors are known to be involved in the pathogenesis of osteoarthritis. Thus, a dependence of osteoarthritis chondrocytes on hypoxia-inducible factor-1alpha to survive and function properly is a reasonable assumption. SUMMARY: Low oxygen tensions and hypoxia-inducible factor-1alpha are important factors in articular chondrocyte behaviour during cartilage homeostasis and osteoarthritis. Hypoxia-inducible factor-1alpha is a highly conserved transcription factor that has key functions in controlling energy generation, cell survival and matrix synthesis by articular and growth-plate chondrocytes.