AbstractPurpose 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-1α in cartilaginous tissues has been published. Growth plates with functionally inactivated hypoxia-inducible factor-1α display great defects in their central areas caused by massive cell death. This very important observation indicates that hypoxia-inducible factor-1α is absolutely necessary for chondrocytes to survive extremely low oxygen tensions. Furthermore, hypoxia-inducible factor-1α 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-1α 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-1α to survive and function properly is a reasonable assumption.Summary
Low oxygen tensions and hypoxia-inducible factor-1α are important factors in articular chondrocyte behaviour during cartilage homeostasis and osteoarthritis. Hypoxia-inducible factor-1α 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.