A nonprostanoid EP4 receptor selective prostaglandin E2 agonist restores bone mass and strength in aged, ovariectomized rats
A nonprostanoid EP4 receptor selective prostaglandin E2 agonist restores bone mass and strength in aged, ovariectomized rats
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DOI：
10.1359/jbmr.051110
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发表时间：
2006-04-01
影响因子：
6.2
通讯作者：
Thompson, DD
中科院分区：
文献类型：
--
作者：
Ke, HZ;Crawford, DT;Thompson, DD
CP432是一种新发现的非前列腺素类EP4受体选择性前列腺素E-2激动剂。CP432刺激骨小梁和皮质骨形成，恢复骨质质量和骨强度。本研究的目的是确定新发现的非前列腺素类EP4受体选择性前列腺素E-2 （PGE(2)）激动剂CP432是否能对骨质减少的老龄去卵巢（OVX）大鼠产生骨合成代谢作用。材料与方法：对OVX治疗8.5个月的12月龄大鼠皮下注射CP432，剂量分别为0.3、1、3 mg/kg/天，持续6周。测定了对骨量、骨形成、骨吸收和骨强度的影响。结果：CP432给药后，OVX大鼠股骨总骨密度均显著升高。CP432完全恢复OVX大鼠第三腰椎椎体骨小梁体积，同时破骨细胞数量和破骨细胞表面呈剂量依赖性减少，矿化表面、矿物质附着率和骨形成率呈剂量依赖性增加（组织参考）。与假手术组和OVX对照组相比，CP432剂量1和3 mg/kg/天显著增加胫骨总组织面积、皮质骨面积、骨膜和皮质内骨形成。与假手术和OVX对照组相比，CP432在所有剂量下均显著且剂量依赖地增加了第五腰椎椎体的极限强度。与假手术和OVX对照组相比，CP432在1和3 mg/kg/天时显著增加股骨干三点弯曲试验中的最大负荷。结论：CP432通过刺激骨形成和抑制骨小梁和皮质表面的骨吸收，完全恢复骨减少、衰老的OVX大鼠骨小梁和皮质的骨量和强度。
CP432 is a newly discovered, nonprostanoid EP4 receptor selective prostaglandin E-2 agonist. CP432 stimulates trabecular and cortical bone formation and restores bone mass and bone strength in aged ovariectomized rats with established osteopenia.Introduction: The purpose of this Study was to determine whether a newly discovered, nonprostanoid EP4 receptor selective prostaglandin E-2 (PGE(2)) agonist, CP432, could produce bone anabolic effects in aged, ovariectomized (OVX) rats with established osteopenia.Materials and Methods: CP432 at 0.3, 1, or 3 mg/kg/day was given for 6 weeks by subcutaneous injection to 12-month-old rats that had been OVX for 8.5 months. The effects on bone mass, bone formation, bone resorption, and bone strength were determined.Results: Total femoral BMD increased significantly in OVX rats treated with CP432 at all doses. CP432 completely restored trabecular bone volume of the third lumbar vertebral body accompanied with a dose-dependent decrease in osteoclast number and osteoclast surface and a dose-dependent increase in mineralizing surface, mineral apposition rate, and bone formation rate-tissue reference in OVX rats. CP432 at 1 and 3 mg/kg/day significantly increased total tissue area, cortical bone area, and periosteal and endocortical bone formation in the tibial shafts compared with both sham and OVX controls. CP432 at all doses significantly and dose-dependently increased ultimate strength in the fifth lumber vertebral body compared with both sham and OVX controls. At 1 and 3 mg/kg/day, CP432 significantly increased maximal load in a three-point bending test of femoral shaft compared with both sham and OVX controls.Conclusions: CP432 completely restored trabecular and cortical bone mass and strength in established osteopenic, aged OVX rats by stimulating bone formation and inhibiting bone resorption on trabecular and cortical surfaces.