A single injection of the anabolic bone agent, parathyroid hormone-collagen binding domain (PTH-CBD), results in sustained increases in bone mineral density for up to 12 months in normal female mice.
A single injection of the anabolic bone agent, parathyroid hormone-collagen binding domain (PTH-CBD), results in sustained increases in bone mineral density for up to 12 months in normal female mice.
复制标题
给正常雌性小鼠注射一次同化骨制剂--甲状旁腺激素-胶原结合域（PTH-CBD），可使其骨矿物质密度在长达 12 个月的时间内持续增加。
DOI：
10.1007/s00223-012-9626-1
复制
发表时间：
2012-09
影响因子：
4.2
通讯作者：
Gensure, Robert C.
中科院分区：
文献类型：
--
作者：
Ponnapakkam, Tulasi;Katikaneni, Ranjitha;Suda, Hirofumi;Miyata, Shigeru;Matsushita, Osamu;Sakon, Joshua;Gensure, Robert C.
甲状旁腺激素（PTH）是最有效的骨质疏松症治疗，但它是唯一有效的，如果每天注射管理。我们将PTH（1-33）融合到胶原蛋白结合结构域（PTH-CBD）以延长其活性，并显示每月给药的合成代谢骨效应。我们测试了该化合物在不同给药途径下的作用持续时间。正常幼龄C57 BL/6 J小鼠接受PTH-CBD（320 μg/kg）的单次腹膜内注射。PTH-CBD治疗的小鼠在6个月时显示骨矿物质密度（BMD）增加22.2%，在12个月时增加12.8%。当通过皮下注射给药时，PTH-CBD再次引起BMD增加，6个月时增加15.2%，12个月时增加14.3%。放射性标记的PTH-CBD在任一给药途径后集中在骨骼和皮肤中。我们进一步研究了PTH-CBD的皮肤效应，组织学分析显示生长期VI毛囊明显增加。无论给药途径如何，单剂量PTH-CBD在正常小鼠中引起BMD持续增加> 10%持续1年，因此显示出作为潜在的骨质疏松症治疗的前景。
Parathyroid hormone (PTH) is the most effective osteoporosis treatment, but it is only effective if administered by daily injections. We fused PTH(1–33) to a collagen binding domain (PTH–CBD) to extend its activity, and have shown an anabolic bone effect with monthly dosing. We tested the duration of action of this compound with different routes of administration. Normal young C57BL/6J mice received a single intraperitoneal injection of PTH–CBD (320 μg/kg). PTH–CBD treated mice showed a 22.2 % increase in bone mineral density (BMD) at 6 months and 12.8 % increase at 12 months. When administered by subcutaneous injection, PTH–CBD again caused increases in BMD, 15.2 % at 6 months and 14.3 % at 12 months. Radiolabeled PTH–CBD was concentrated in bone and skin after either route of administration. We further investigated skin effects of PTH–CBD, and histological analysis revealed an apparent increase in anagen VI hair follicles. A single dose of PTH–CBD caused sustained increases in BMD by >10 % for 1 year in normal mice, regardless of the route of administration, thus showing promise as a potential osteoporosis therapy.
登录
查看更多内容
影响因子：
6.2
作者：
Burge, Russel;Dawson-Hughes, Bess;Tosteson, Anna
通讯作者：
Tosteson, Anna
影响因子：
4.1
作者：
Beamer, WG;Donahue, LR;Baylink, DJ
通讯作者：
Baylink, DJ
影响因子：
3.1
作者：
Tamai, E;Ishida, T;Okabe, A
通讯作者：
Okabe, A
影响因子：
4
作者：
Subbiah, V.;Madsen, V. S.;Ludwig, J. A.
通讯作者：
Ludwig, J. A.
影响因子：
15.9
作者：
Ahima, RS;Dushay, J;Flier, JS
通讯作者：
Flier, JS