Abstract
Calcitonin has been recently shown to have a direct protective effect on articular cartilage against joint degenerative disease. It has been proposed that calcitonin might act through the calcitonin receptor (CTR) to activate the cyclic AMP pathway and protect type II collagen degradation. In this study, we examined the presence of the CTR in human articular cartilage and chondrocytes and investigated the potential pharmacological effects and transduction pathway of salmon calcitonin in human chondrocytes.
Five human articular cartilage samples were examined for the expression of the CTR by polymerase chain reaction (PCR), immunostaining and Western blotting. Cyclic AMP levels in human chondrocyte stimulated with salmon calcitonin were measured by ELISA. The effect of salmon calcitonin on the gene expression profiles, including aggrecan, type II collagen, matrix metalloproteinase (MMP)-1, MMP-3 and MMP-13, of human chondrocytes was also examined by Real-time PCR.
It was shown that CTR was not detectable in human cartilage and chondrocytes. The cAMP level in human chondrocytes in vitro was significantly increased by forskolin (100μM) by > 10 fold (P< 0.001), but was not induced by salmon calcitonin (10^-7M, 10^-8M, 10^-9M). Real-time PCR demonstrated that salmon calcitonin tended to reduce the gene expression of MMPs, yet without statistical significance. In contrast to previous reports, our data showed that human cartilage and chondrocytes do not express calcitonin receptors. There was no direct effect of salmon calcitonin on human chondrocytes.
The result suggests that the chondroprotective effect of calcitonin observed in vivo may be indirect via its effect on subchondral bone resorptive activity.
Correspondence should be addressed to David Haynes, PhD, Senior Lecturer, President ANZORS, at Discipline of Pathology, School of Medical Sciences, University of Adelaide, SA, 5005, Australia
