ANALYSIS OF HUMAN ARTICULAR CHONDROCYTE CD44 ISOFORM EXPRESSION AND FUNCTION IN HEALTH AND DISEASE

Interactions between articular chondrocytes and components of the extr acellular matrix are of potential importance in the normal function of cartilage and in the pathophysiology of arthritis. Little is known of the basis of these interactions, but cell adhesive molecules such as CD44 are likely to be involved, Immunohistology using six well-charact erized anti-CD44 monoclonal antibodies demonstrated standard CD44 isof orm (CD44H) expression by all chondrocytes in normal and osteoarthroti c (OA) cartilage but absence of the CD44E variant. Polymerase chain re action (PCR) of reverse transcribed mRNA from monolayer cultures of no rmal and OA chondrocytes using primer sequences which span the region containing variably spliced exons produced a predominant band represen ting the standard form of CD44, which lacks the variable exons 6-15 (v 1-v10), No product was seen at the expected size of the epithelial var iant of CD44 (CD44v8-10). Use of exon-specific primers, however, showe d expression of variant exons resulting in multiple minor isoforms. St andard CD44 was also shown to be the predominantly expressed isoform i dentified by immunoprecipitation, but human articular chondrocytes did not adhere to hyaluronan in vitro. Chondrocyte CD44 may function as a n adhesion receptor for other matrix molecules such as fibronectin or collagen.