INTEGRIN EXPRESSION ON CHONDROCYTES - CORRELATIONS WITH THE DEGREE OFCARTILAGE DAMAGE IN HUMAN OSTEOARTHRITIS

Objective. To verify the distribution of different types of pi integri n on the plasma membrane of chondrocytes and to correlate the pattern of integrin expression to the severity of osteoarthritis (OA). Methods . The articular cartilage often OA patients who had undergone surgical knee replacement for ''genu varum'' were studied. The cartilage Mas s eparated into three zones that macroscopically and microscopically sho wed a decreasing degree of anatomic lesions. After enzymatic digestion , the isolated chondrocytes were immediately challenged with monoclona l antibodies against the beta(1), alpha(1-6) and alpha(v) chains. The phenotypic study was paralleled by a cell cycle analysis performed by flow cytometry on chondrocytes stained with propidium iodide. Results. Chondrocytes isolated from the articular cartilage of osteoarthritic patients expressed, in different percentages, all the alpha chains (al pha(1-6) and alpha(v)) of the beta(1) integrins. The a chain most freq uently expressed was alpha(1), followed by alpha(3), alpha(5), alpha(2 ) and alpha(v), with lesser amounts of alpha(4) and alpha(6). The beta (1) chain was expressed (on average) on the 40% of the chondrocytes re gardless of the zone they were isolated from. Differential phenotypic analysis of the three zones showed that beta(1) integrins correlate in versely with the severity of the anatomic lesions and the cycle phase of the chondrocytes (the G0/G1 phase prevailed in the anatomically nor mal cartilage of the least damaged zone, and the S-phase in the most d amaged zone). Conclusions. This study provides evidence of the existen ce of beta(1) integrins on the surface of chondrocytes from human OA c artilage, all of the a chains being represented, although in different percentages. Moreover, an inverse correlation was demonstrated betwee n the severity of the anatomical changes found in the zones and the ph enotypic/metabolic changes ofthe cells. These results, together with t he well known inside-out signaling function of the adhesion molecules, highlight the key role of matrix interactions in the pathogenesis of the anatomic changes in OA.