Effects of Cyclosporin A on the Epiphyseal Plate Growth in Rats

Kim, H J; Kim, O J; Hoang, Y C; Shin, J H; Park, H O; Kim, M S; Lee, E J; Kim, S H

Abstract

Cyclosporin A (CsA), hydrophobic cyclic peptide composed of 11 amino acids has been currently used in immunosuppression by its ability to inhibit cytokine release. The inhibition of cytokine release can secondarily affect on bone metabolism, modelling and remodelling. Current concept suggests that CsA can induce osteopenia by stimulating both bone formation and resorption. But many reports have not been coincident each other in respect of its action mechanism in vivo and in vitro. The present study was performed to clarify CsA effects on bone growth using cell proliferation assay, gene expression in vitro using MC3T3 cell line. Histomorphomertical data were obtained from knee joint in vivo after 3, 7 and 14 days of each CsA treatment. MC3T3-E1 cell proliferation was inhibited by the treatment of CsA 1,000 ng/ml and 1,500 ng/ml in concentration for 1 and 3 days. CollagenI (alpha)1 gene expression was decreased by the treatment in a dose dependant manner, whereas ALP expression was stable in every concentration of treatment. Histomorphometrical data analysis such as length of hypertrophied and proliferating cartilage layer, area of secondary ossification center, trabecular bone length underneath the epiphyseal plate and finally chondroclast number and size showed that most of the measurements were decreased especially after 2 weeks of CsA treatment. These results suggested that CsA treatment can directly affect on osteoblasts, inhibiting normal bone growing processes.