HUMAN CARTILAGE GP-39, A MAJOR SECRETORY PRODUCT OF ARTICULAR CHONDROCYTES AND SYNOVIAL-CELLS, IS A MAMMALIAN MEMBER OF A CHITINASE PROTEINFAMILY

One of the major secreted proteins of human articular chondrocytes in monolayer or explant culture and of synovial fibroblasts is a glycopro tein with an apparent molecular weight of approximately 39,000, referr ed to as human cartilage glycoprotein-39 (HC gp-39). The protein was p urified, and its complete cDNA sequence was determined. It contained a n open reading frame coding for a 383-amino acid long peptide. Compari son of the deduced amino acid sequence with known sequences revealed t hat HC gp-39 contained regions displaying significant homology with a group of bacterial and fungal chitinases and a similar enzyme found in the nematode, Brugia malayi. In addition significant homologies were observed with three mammalian secretory proteins of as yet unknown fun ction, suggesting that a related protein family exists in mammals. The human protein does not possess any glycosidic activity against chitin ase substrates, arguing against any function as an endoglycosidase wit h specificity for N-acetylglucosamine. Analysis by Northern blotting a nd by reverse transcription/polymerase chain reaction showed mRNA for HC gp-39 to be present in human articular chondrocytes as well is in l iver, while mRNA was undetectable in muscle tissues, lung, pancreas, m ononuclear cells, or fibroblasts. Neither the protein nor mRNA for HC gp-39 was detectable in normal newborn or adult human articular cartil age obtained at surgery, while mRNA for HC gp-39 was detectable both i n synovial specimens and in cartilage obtained from patients with rheu matoid arthritis. These observations suggest that the expression of HC gp-39 may be related to a response of these cells to an altered tissu e environment.