NG2/HMPG modulation of human articular chondrocyte adhesion to type VI collagen is lost in osteoarthritis

NG2/human melanoma proteoglycan (HMPG) is a chondroitin sulphate proteoglyc an (CSPG), expressed by chondrocytes in fetal and in normal and osteoarthri tic (OA) adult articular cartilage. NG2/HMPG is a receptor for extracellula r matrix proteins, including type VI collagen, and regulates fill integrin binding to fibronectin. This study was undertaken to identify whether NG2/H MPG had similar activities in human articular chondrocytes (HACs). Normal a nd OA adult HAC adhesion to fibronectin, type II or type VI collagen was as sessed using a methylene blue assay. The requirement for integrins, NG2/HMP G, and integrin-associated signalling molecules was investigated using anti -beta1 integrin and anti-HMPG antibodies and pharmacological inhibitors of signalling molecules. The adhesion of normal and OA HACs to fibronectin, ty pe II and type VI collagen was beta1 integrin-dependent. Normal HAC adhesio n to type V1 collagen was stimulated by anti-HMPG antibodies. This effect w as inhibited by pertussis toxin. Anti-HMPG antibodies had no effect on OA c hondrocyte adhesion to type VI collagen, or on normal and OA cell adhesion to fibronectin and type II collagen. The results show that NG2/HMPG modulat es integrin-mediated interactions of normal HACs with type VI collagen. Los s of this activity may be of importance in the progression of osteoarthriti s. Copyright (C) 2001 John Wiley & Sons, Ltd.