Expression and activity of articular cartilage hyaluronidases

The glycosaminoglycan hyaluronan is an important component of the extracellular matrix of articular cartilage, contributing to both the structural and functional integrity of this highly specialized tissue. Hyaluronan is known to be synthesized and turned over by the resident chondrocytes, although the mechanisms involved in hyaluronan degradation are not precisely defined. Recently, the cDNA sequences of extracellular hyaluronidases present on spermatazoa and in human serum have been reported, and we have utilized these data to investigate the expression and activity of these and/or related enzymes by articular cartilage chondrocytes. By using "gene-homology" RT-PCR techniques, three hyaluronidase isozymes were found to be expressed by chondrocytes, and hyaluronidase activity was detected in cell membrane extracts and conditioned media from chondrocyte monolayer cultures following acidification to pH 4.5 or pH 3.7. In addition, the levels of mRNA for two of the chondrocyte hyaluronidases were upregulated by IL-1 and TNF stimulation, thereby implicating cartilage-derived hyaluronidase activity as a factor contributing to cytokine-induced extracellular matrix degradation during synovial joint disease.