Expression of ADAMTS homologues in articular cartilage

Abstract

Articular chondrocytes possess the capacity to express a number of ADAM (A Disintegrin And Metalloproteinase) family members, thereby implicating a role for such proteins in the turnover of cartilage extracellular matrix molecules. Recently, the sequence for the human orthologue of an "aggrecanase" isolated from bovine nasal cartilage has been elucidated, and the recombinant protein product shown to be capable of cleaving aggrecan specifically at the relevant peptide bonds which are hydrolyzed in situ during cartilage degradation. The sequence for the human "aggrecanase" exhibits homology with that of murine ADAMTS-1, an ADAM with thrombospondin type I motifs. In the present study we have identified additional ADAMTS homologues and have examined their mRNA expression profiles in freshly excised human articular cartilage and in human cartilage explant cultures stimulated with IL-1, TNF-alpha, or retinoic acid, agents which enhance "aggrecanase" activity in vitro. Significantly, cartilage exposed to retinoic acid showed a marked increase in the release of "aggrecanase"-generated aggrecan catabolites with no concomitant increase in mRNA levels for any of the ADAMTS homologues investigated. These findings indicate that enhanced "aggrecanase" activity, which may be attributed to known ADAMTS homologues, may be predominantly regulated by post-transcriptional mechanism(s), and may raise the possiblility for the existence of other as yet unidentified "aggrecanase(s)."