免疫抑制剤サイクロスポリンAがラット骨代謝に及ぼす影響

Cyclosporin A (CsA) is used as an immunosuppressive agent and its one of prominent side effects is an induction of osteoporosis. The purpose of this study was to investigate the effect of CsA on bone metabolism to elucidate the mechanisms of CsA-induced osteoporosis. Fifteen-day-old rats were fed a powdered-diet containing or lacking CsA for 8 to 30 days. On days 8, 16 and 30, tibiae, bone marrows, and plasma were collected for morphological and biochemical assays. During experimental periods, there was no influence of CsA on the full length of tibia and body weight. Three dimensional micro CT analysis revealed that the three dimensional trabecular bone volume of proximal tibia treated with CsA was not changed on day 8 but it was decreased on days 16 and 30 showing osteoporotic bone resorption. Histological analysis from decalcified section revealed that the volume of bone was decreased by CsA on days 16 and 30 whereas no change on day 8. On day 16, the number of osteoclasts and osteoblasts in CsA-treated rats were significantly increased than that in the controls. Plasma calcium level was normally maintained during experimental periods in both groups. Plasma parathyroid hormone (PTH) and osteocalcin (OCN) levels in CsA-treated rats were increased on day 8 and the levels were decreased to the control levels on days 16 and 30. Northern blot analysis using bone marrow cells revealed that the CsA-treated group showed the increased mRNA levels of OCN, OPN, and cathepsin K on day 8. On day 16, no significant differences of these mRNA levels were observed between CsA-treated and the control groups. The elevation of the parameters on day 8 may possibly reflect the functional increase of bone metabolism in rat long bones, followed by the appearance of bone resorption on day 16. These findings suggest that bone resorption observed in CsA-treated rats is a result of high turnover of bone metabolism and that the active bone remodeling may be induced by the elevation of plasma PTH.

公開日:2010年1月24日で登録したコンテンツは、国立情報学研究所において電子化したものです。