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新型甲状旁腺激素片段hPTH-(1-31)NH2(奥司他丁)对去卵巢大鼠股骨小梁骨生长的刺激作用

Stimulation of the growth of femoral trabecular bone in ovariectomized rats by the novel parathyroid hormone fragment, hPTH-(1-31)NH2 (Ostabolin).

作者信息

Whitfield J F, Morley P, Willick G E, Ross V, Barbier J R, Isaacs R J, Ohannessian-Barry L

机构信息

Institute for Biological Sciences, National Research Council of Canada, Ottawa, Ontario.

出版信息

Calcif Tissue Int. 1996 Feb;58(2):81-7. doi: 10.1007/BF02529728.

Abstract

The human parathyroid hormone, hPTH-(1-84), and its hPTH-(1-34) fragment are promising anabolic agents for treating osteoporosis because they can strongly stimulate the production of biomechanically effective cortical and trabecular bone in osteopenic ovariectomized (OVX) rats and trabecular bone in osteoporotic postmenopausal humans. The ideal PTH fragment for treating osteoporosis would be the smallest and functionally simplest fragment that activates only one signal mechanism and still strongly stimulates trabecular bone growth. A new PTH fragment, hPTH-(1-31)NH2, which only stimulates adenylyl cyclase instead of stimulating both adenylyl cyclase and phospholipase-C as do hPTH-(1-84) and hPTH-(1-34), is this minimum, high-potency anabolic fragment. hPTH-(1-31)NH2 (which we have named Ostabolin) can greatly thicken trabeculae and increase the dry weight and calcium content of trabecular bone in the distal femurs of osteopenic, young, sexually mature OVX Sprague-Dawley rats when injected subcutaneously each day for 6 weeks at doses between 0.4 and 1.6 nmole/100 g of body weight.

摘要

人甲状旁腺激素hPTH-(1-84)及其hPTH-(1-34)片段是治疗骨质疏松症的有前景的促合成代谢药物,因为它们能强烈刺激骨质减少的去卵巢(OVX)大鼠产生具有生物力学效应的皮质骨和小梁骨,并刺激绝经后骨质疏松症患者的小梁骨生长。治疗骨质疏松症的理想甲状旁腺激素片段应是最小且功能最简单的片段,它仅激活一种信号机制,同时仍能强烈刺激小梁骨生长。一种新的甲状旁腺激素片段hPTH-(1-31)NH2,它只刺激腺苷酸环化酶,而不像hPTH-(1-84)和hPTH-(1-34)那样同时刺激腺苷酸环化酶和磷脂酶-C,是这种最小的高效促合成代谢片段。当以0.4至1.6纳摩尔/100克体重的剂量每天皮下注射6周时,hPTH-(1-31)NH2(我们将其命名为Ostabolin)可使骨质减少、年轻、性成熟的OVX Sprague-Dawley大鼠股骨远端的小梁骨显著增厚,并增加小梁骨的干重和钙含量。

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