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TAK-778通过雌激素受体依赖通道诱导去卵巢大鼠的成骨能力

发表时间:2013-06-15  浏览量:1178  下载量:336
全部作者: 刘鹏程,蔡明
作者单位: 同济大学附属第十人民医院骨科
摘 要: 目的:使用去卵巢(ovariectomized, OVX)大鼠模型检测TAK-778是否依赖雌激素受体(estrogen receptor,ER)通路发挥诱导成骨作用。方法:OVX大鼠造模2周后口服TAK-778和/或他莫昔芬(tamoxifen)3月余,溶液组(vehicle)和假手术组(sham)作为对照组。测量腰椎骨矿物密度(bone mineral density,BMD)、L3椎体矢状二维图、骨形成率(bone formation rates,BFR)、血清钙及骨钙素水平。结果:与vehicle相比,TAK-778显著提高了BMD、血清钙和骨钙素及BFR水平。研究还发现,使用雌激素受体拮抗剂tamoxifen可以明显抑制TAK-778诱导的上述指标的增加;Micro-CT扫描显示经TAK-778处理的OVX大鼠的骨结构模型指数(structure model index, SMI)、骨体积/组织体积(bone volume/tissue volume, BV/TV)和骨小梁厚度(trabecular thickness, Tb.Th)增加,骨小梁间距(trabecular separation/spacing, Tb.Sp)缩小;tamoxifen与TAK-778结合抑制了上述观察指标。结论:TAK-778通过雌激素依赖受体介导的信号通路增强OVX大鼠的成骨能力。
关 键 词: 外科学;成骨;TAK-778;他莫昔芬;雌激素受体;去卵巢大鼠
Title: TAK-778 induces osteogenesis in ovariectomized rats through an estrogen receptor-dependent pathway
Author: LIU Pengcheng, CAI Ming
Organization: Department of Orthopedics, Shanghai Tenth People’s Hospital, Tongji University
Abstract: Objective: To test if TAK-778 induces osteogenesis through an estrogen receptor (ER) dependent pathway using an ovariectomized (OVX) rat model. Methods: Two weeks after test animals underwent ovariectomy, TAK-778 and/or tamoxifen was administered orally over 3 months. Vehicle-treated and sham-operated rats were served as controls. The bone mineral density (BMD) of the lumbar vertebrae and sagittal two-dimensional images of the L3 vertebral body were measured. In addition, bone formation rates (BFR) and serum calcium and osteocalcin levels were investigated. Results: TAK-778 significantly increased BMD, serum calcium and osteocalcin levels, and BFR when comparing to those of the vehicle-treated group. However, tamoxifen clearly inhibited the increase in these parameters induced by TAK-778. In addition, micro-CT tomography scanning showed that treatment with TAK-778 increased the structure model index (SMI), bone volume/tissue volume (BV/TV), and trabecular thickness (Tb.Th) parameters, while decreased the trabecular spacing (Tb. Sp) in OVX rats. Tamoxifen suppressed these effects when was combined with TAK-778. Conclusion: Taken together, the present study showed that TAK-778 enhanced osteogenesis in ovariectomized rats through an estrogen receptor-dependent pathway.
Key words: surgery; osteogenesis; TAK-778; tamoxifen; estrogen receptor; ovariectomized rats
发表期数: 2013年6月第11期
引用格式: 刘鹏程,蔡明. TAK-778通过雌激素受体依赖通道诱导去卵巢大鼠的成骨能力[J]. 中国科技论文在线精品论文,2013,6(11):1027-1032.
 
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