CHONDROCYTES ARE REGULATED BY CELLULAR ADHESION THROUGH CD44 AND HYALURONIC-ACID PATHWAY

The articular cartilage consists of resident chondrocytes embedded wit hin the extracellular matrix which contains several components such as collagen and hyaluronic acids (HA), CD44 is a major cell surface rece ptor for HA and is homologous to cartilage-link proteins, Although CD4 4 is present in cartilage, it is not clear if chondrocytes adhere to H A through CD44 or whether such adhesion changes the function of chondr ocytes, We studied the molecular mechanisms of CD44-related chondrocyt e adhesion to HA and the effects of such adhesion on chondrocyte funct ion, Experiments were performed using the human chondrosarcoma-derived chondrocyte-like cell line HCS-2/8. Our results shoved that (a) HCS-2 /8 cells highly expressed CD44; (b) HCS-2/8 cells efficiently adhered to HA without any stimuli; (c) monoclonal antibody (mAb)-blocking stud ies indicated that adhesion of HCS-2/8 cells to HA was mainly mediated by the CD44/HA pathway; (d) cellular adhesion to HA increased the pro liferation of HCS-2/8 cells, independent of transforming growth factor -beta (TGF-beta), but this was inhibited by CD44 mAb; (e) the adhesion of chondrocytes to HA also induced c-myc mRNA expression and this was also inhibited by CD44 mAb; and (f) the adhesion of cells to HA augme nted TGF-beta mRNA expression, a process also reduced by CD44 mAb, Thu s, HCS-2/8 cells effectively adhered to HA through cell surface CD44, The adhesion was also involved in cellular signaling which induced cel lular proliferation and expression of c-myc mRNA as well as TGF-beta m RNA expression within the cells, Our results indicate that CD44 on cho ndrocytes plays an important role in normal and abnormal functions of cartilage through its adhesion to HA, which induces a variety of stimu latory signals to regulate chondrocyte proliferation as well as matrix synthesis in cartilage microenvironment.