辛伐他汀对PTHrP诱导破骨细胞形成及小鼠颅盖骨代谢的影响

Effect of simvastatin on PTHrP stimulated osteoclastic resorption and anabolism of murine calvarium

目的:探讨辛伐他汀对体外甲状旁腺素相关肽(PTHrP)诱导小鼠的破骨细胞骨吸收功能的作用及其小鼠骨代谢的影响。方法:采用PTHrP诱导小鼠骨髓细胞培养破骨细胞和小鼠颅盖骨培养体系,检测辛伐他汀作用8d后破细胞骨数目和培养上清钙的变化;检测小鼠颅盖骨培养上清碱性磷酸酶和钙含量,组织学观察小鼠颅盖骨形态学变化。结果:辛伐他汀体外可明显抑制PTHrP诱导小鼠的破骨细胞骨吸收陷窝的形成及培养上清钙的释放,辛伐他汀体外可增强小鼠颅盖骨培养上清碱性磷酸酶的活性,组织学观察到辛伐他汀使小鼠颅盖骨矿化增强。结论:辛伐他汀体外不仅可促进小鼠颅盖骨的成骨活性,并且可明显抑制PTHrP诱导小鼠的破骨细胞骨吸收功能,对骨吸收性疾病有着重要的防治作用。

Objective：To study the effect of simvastatin on PTHrP stimulated osteoclastic resorption of murine calvarium and bone anabolism in vitro. Methods：Osteoclasts were isolated from bone marrow of Balb/C mice, cultured and identified. Calvaria of the new born Balb/C mice were cultured with PTHrP at 45 ng/ml and/or simvastatin at 10^-7 - 10^-5 mol/L for 8 d. Ca^2＋ and ALP in the culture supernatent were measured by atom spectrophotometer and automatic biochemical analyzer respectively. The bones were examined histologically. Results： Simvastatin at 10^-7 - 10^-5 mol/L inhibited osteoclast formation and the osteoclastic bone resorption stimulated by PTHrP in vitro and reduced the release of Ca^2＋ from the cultured osteoclasts in a dose-dependent manner. Simvastatin increased the ALP activities and bone mineralization of murines calvaria cultured in vitro. Conclusions：Simvastatin may inhibit the osteoclasric resorption stimulated by PTHrP and promote bone mineralization in vitro.