Anti-Fas-induced apoptosis in chondrocytes reduced by hyaluronan: evidence for CD44 and CD54 (intercellular adhesion molecule 1) invovement

To investigate the in vitro effect of therapeutic hyaluronan (HA) of 500-730 kd on anti-Fas-induced apoptosis of chondrocytes from osteoarthritis (OA) patients, and to assess its mechanism of action by analyzing the role of the 2 HA receptors, CD44 and CD54 (intercellular adhesion molecule 1 [ICAM-1]). Both quantitative tests demonstrated that anti-Fas significantly induced apoptosis of isolated OA chondrocytes. HA at 1,000 microg/ml significantly reduced the anti-Fas-induced apoptosis of chondrocytes but did not affect spontaneous chondrocyte apoptosis. These data were also confirmed by TUNEL staining and by electron microscopy morphologic evaluation. The antiapoptotic effects of HA on anti-FAS-induced chondrocyte apoptosis were significantly decreased by both anti-CD44 (mean +/- SD 57 +/- 12% inhibition) and anti-ICAM-1 (31 +/- 22% inhibition). The mixture of the 2 antibodies had an additive effect, since the rate of inhibition increased to 87 +/- 13%. These data demonstrate that 500-730-kd HA exerts an antiapoptotic effect on anti-FAS-induced chondrocyte apoptosis by binding its specific receptors (CD44 and ICAM-1). Furthermore, this HA fraction may be able to slow down chondrocyte apoptosis in OA by regulating the processes of cartilage matrix degradation