Hypoxia and HIF-1alpha in osteoarthritis.

We have previously shown that functional inactivation of hypoxia-inducible factor-1alpha (HIF-1alpha) in growth-plate chondrocytes will dramatically inhibit anaerobic energy generation and matrix synthesis. Using immunohistochemistry, we have now analyzed the spatial distribution of HIF-1alpha and its target genes in normal cartilage and in cartilage from knee joints with osteoarthritis. We detected HIF-1alpha and its target genes in both types of cartilage. In cartilage from joints with osteoarthritis, the number of HIF-1alpha-, Glut-1-, and PGK-1-stained chondrocytes increased with the severity of osteoarthritis. Activated matrix synthesis and strongly decreased oxygen levels are hallmarks of osteoarthritic cartilage. Thus, we assume that chondrocytes are depending on the adaptive functions of HIF-1alpha in order to maintain ATP levels and thereby matrix synthesis during the course of osteoarthritis.