Local injection of a single dose of simvastatin augments osteoporotic bone mass in ovariectomized rats
Local injection of a single dose of simvastatin augments osteoporotic bone mass in ovariectomized rats
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DOI：
10.1007/s00774-013-0496-z
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发表时间：
2014-05
影响因子：
3.3
通讯作者：
Ning Yang;Yueyi Cui;Jie Tan;Xin Fu;Xiaoguang Han;H. Leng;Chunli Song
中科院分区：
文献类型：
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作者：
Ning Yang;Yueyi Cui;Jie Tan;Xin Fu;Xiaoguang Han;H. Leng;Chunli Song
本研究的目的是评估局部注射单剂量辛伐他汀作为强化靶骨的策略的效果并探讨其机制。去卵巢大鼠股骨注射辛伐他汀5 mg或10 mg，尾椎注射辛伐他汀1 mg或2 mg，等量注射赋形剂作为对照。分别于股骨注射后1个月、5个月和椎骨注射后12天测定骨密度、骨显微结构和强度。用组织学和免疫组织化学方法检测骨量、脂肪细胞数和Runx2的表达。与对照组相比，辛伐他汀在两个时间点均显著增加股骨骨密度、骨体积分数(BV/TV)、改善骨显微结构参数和骨强度(P均<0.01)。辛伐他汀治疗的股骨含有较少的脂肪细胞和较高的Runx2表达。对于尾椎，与对照组相比，辛伐他汀显著改善了BV/TV、骨显微结构和骨强度(均P<0.01)。综上所述，局部单次注射辛伐他汀可在骨质疏松骨中诱导起效早、持续时间长的骨强化，显著改善骨密度、骨微结构和生物力学强度。辛伐他汀可诱导Runx2的表达，而Runx2可能具有诱导成骨和抑制脂肪生成的作用，是增加骨量的潜在机制。
The aim of this study was to evaluate the effects and explore the mechanism of a local injection of a single dose of simvastatin as a strategy to strengthen target bone. Simvastatin was injected into the femurs (5 or 10 mg) or caudal vertebrae (1 or 2 mg) of ovariectomized rats, with an equal volume of vehicle injected as a control. Bone mineral density (BMD), bone microstructure and strength were evaluated at 1 and 5 months post-injection for the femurs and at 12 days post-injection for the vertebrae. Bone mass, adipocyte numbers and Runx2 expression were also examined using histology and immunohistochemistry. Compared with controls, simvastatin significantly increased BMD, bone volume fraction (BV/TV), improved bone microstructural parameters and bone strength in the femurs at both time points (allP< 0.01). Simvastatin-treated femurs contained fewer adipocytes and a higher Runx2 expression. For the caudal vertebrae, simvastatin significantly improved BV/TV, bone microstructures, and bone strength (allP< 0.01) as compared with controls. In conclusion, local injection of a single dose of simvastatin induces early onset and long-lasting bone augmentation in osteoporotic bone, significantly improving BMD, and bone microstructure and biomechanical strength. Simvastatin induces Runx2 expression, which may function to induce osteogenesis and inhibit adipogenesis as an underlying mechanism to augment bone mass.