Parathyroid hormone 1-34 and skeletal anabolic action: The use of parathyroid hormone in bone formation.
Parathyroid hormone 1-34 and skeletal anabolic action: The use of parathyroid hormone in bone formation.
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DOI：
10.1302/2046-3758.61.bjr-2016-0085.r1
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发表时间：
2017-01
影响因子：
4.6
通讯作者：
Blunn G
中科院分区：
文献类型：
--
作者：
Osagie-Clouard L;Sanghani A;Coathup M;Briggs T;Bostrom M;Blunn G
在人类和动物研究中，间歇性给予甲状旁腺激素（PTH 1 - 34）已显示出促进骨形成。激素及其类似物刺激骨形成和再吸收，因此低剂量的激素及其类似物目前在临床上用于治疗严重的骨质疏松症。通过改变暴露的持续时间，甲状旁腺激素可以调节基因，导致在所谓的“合成代谢窗口”内增加骨形成。所涉及的成骨机制是多种的，影响骨祖细胞、成骨细胞、骨细胞和干细胞生态位的刺激，并最终导致成骨细胞活化增加、成骨细胞凋亡减少、Wnt/β-连环蛋白信号转导上调、干细胞动员增加和RANKL/OPG通路介导。正在进行的研究，通过“耦合”和“非耦合”机制对骨形成的影响，进一步强调了间歇性PTH对皮质骨和松质骨的影响。鉴于连续PTH的主要分解代谢作用，本文综述了间歇性PTH 1 - 34的骨骼作用及其作用机制。引用此文章：L。Osagie-Clouard，A. Sanghani，M. Coathup，T. Briggs，M. Bostrom，G.布伦甲状旁腺激素1 - 34和骨骼合成代谢作用：甲状旁腺激素在骨形成中的作用。骨关节研究2017; 6：14 - 21。DOI：10.1302/2046 - 3758.61.BJR-2016 - 0085.R1。
Intermittently administered parathyroid hormone (PTH 1-34) has been shown to promote bone formation in both human and animal studies. The hormone and its analogues stimulate both bone formation and resorption, and as such at low doses are now in clinical use for the treatment of severe osteoporosis. By varying the duration of exposure, parathyroid hormone can modulate genes leading to increased bone formation within a so-called ‘anabolic window’. The osteogenic mechanisms involved are multiple, affecting the stimulation of osteoprogenitor cells, osteoblasts, osteocytes and the stem cell niche, and ultimately leading to increased osteoblast activation, reduced osteoblast apoptosis, upregulation of Wnt/β-catenin signalling, increased stem cell mobilisation, and mediation of the RANKL/OPG pathway. Ongoing investigation into their effect on bone formation through ‘coupled’ and ‘uncoupled’ mechanisms further underlines the impact of intermittent PTH on both cortical and cancellous bone. Given the principally catabolic actions of continuous PTH, this article reviews the skeletal actions of intermittent PTH 1-34 and the mechanisms underlying its effect. Cite this article: L. Osagie-Clouard, A. Sanghani, M. Coathup, T. Briggs, M. Bostrom, G. Blunn. Parathyroid hormone 1-34 and skeletal anabolic action: The use of parathyroid hormone in bone formation. Bone Joint Res 2017;6:14–21. DOI: 10.1302/2046-3758.61.BJR-2016-0085.R1.