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 studied. 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 activity, measured using a radiolabeled type II collagen, was inhibited by CT in a dose-dependent manner. However, CT had no effect on the total collagenolytic activity assayed after APMA activation. Stromelysin and plasmin activity, measured by degradation of casein and a synthetic substrate, were also unaffected by CT. Chondrocyte phospholipase A2 activity, assayed using a labeled specific substrate, was decreased by CT. Chondrocyte pre-incubation with CT significantly decreased the cell binding of labeled TNF alpha, but did not affect IL-1 beta cell binding. Attachment of chondrocytes on fibronectin was markedly stimulated by CT, while attachment to type II collagen was not. Significant effects were obtained using at least 2 or 5 ng/ml of CT. CT appears to decrease collagenolytic activity by decreasing its activation and/or increasing its inhibition by tissue inhibitors of metalloproteinases (TIMP). CT might act on osteoarthritic chondrocyte activation via mechanisms such as phospholipase A2 activity, human necrosis factor-alpha or fibronectin receptor expression.
Hellio
M P
MP
Claude Bernard University, Hôpital Edouard Herriot, Lyon, France.
Peschard
M J
MJ
Cohen
C
C
Richard
M
M
Vignon
E
E
D002116:Calcitonin / Q000494:pharmacology*; D002358:Cartilage, Articular / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D002448:Cell Adhesion / Q000187:drug effects; D018929:Cell Culture Techniques; D017364:Collagenases / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006801:Humans; D061965:Matrix Metalloproteinase Inhibitors; D010003:Osteoarthritis / Q000201:enzymology* / Q000473:pathology; D010741:Phospholipases A / Q000037:antagonists & inhibitors* / Q000378:metabolism; D054467:Phospholipases A2
D016207:Cytokines; D061965:Matrix Metalloproteinase Inhibitors; D002116:Calcitonin; D010741:Phospholipases A; D054467:Phospholipases A2; D017364:Collagenases