CALCITONIN INHIBITS PHOSPHOLIPASE-A2 AND COLLAGENASE ACTIVITY OF HUMAN OSTEOARTHRITIC CHONDROCYTES

Calcitonin (CT) is a known potent inhibitor of bone resorption but its effect on cartilage enzymatic degradation has been incompletely studi ed. Salmon CT, at a concentration of 0, 0.1, 0.25, 0.5, 2.5 and 50 ng/ ml, was added at 24 or 72 h to the culture medium of chondrocytes from human osteoarthritic hips and knees. The spontaneous collagenolytic a ctivity, measured using a radiolabeled type II collagen, was inhibited by CT in a dose-dependent manner. However, CT had no effect on the to tal collagenolytic activity assayed after APMA activation. Stromelysin and plasmin activity, measured by degradation of casein and a synthet ic substrate, were also unaffected by CT. Chondrocyte phospholipase A2 activity, assayed using a labeled specific substrate, was decreased b y CT. Chondrocyte pre-incubation with CT significantly decreased the c ell binding of labeled TNF alpha, but did not affect IL-1 beta cell bi nding. Attachment of chondrocytes on fibronectin was markedly stimulat ed by CT, while attachment to type II collagen was not. Significant ef fects were obtained using at least 2 or 5 ng/ml of CT. CT appears to d ecrease collagenolytic activity by decreasing its activation and/or in creasing its inhibition by tissue inhibitors of metalloproteinases (TI MP). CT might act on osteoarthritic chondrocyte activation via mechani sms such as phospholipase A2 activity, human necrosis factor-ct or fib ronectin receptor expression.