Regulation of Bone Remodeling by Parathyroid Hormone
Regulation of Bone Remodeling by Parathyroid Hormone
复制标题
DOI：
10.1101/cshperspect.a031237
复制
发表时间：
2018-08-01
影响因子：
5.4
通讯作者：
Kronenberg, Henry M.
中科院分区：
文献类型：
--
作者：
Wein, Marc N.;Kronenberg, Henry M.
甲状旁腺激素（PTH）通过多种细胞和分子机制对骨骼稳态产生深远影响。持续性甲状旁腺功能亢进导致骨量净丢失，尽管加速了成骨细胞的骨形成。使用PTH类似物的间歇治疗代表了唯一的食品和药物管理局（FDA）批准的骨合成代谢性骨质疏松症治疗策略。功能性PTH受体存在于成骨细胞谱系的细胞上，范围从早期骨骼干细胞到基质包埋的骨细胞。此外，破骨细胞的骨重建释放出骨基质中存在的潜在生长因子。在这里，我们将提供一个概述的多种细胞和分子机制，通过PTH影响骨稳态。值得注意的是，连续性与间歇性的净骨骼效应可以显著不同。在可能的情况下，我们将强调持续性甲状旁腺功能亢进导致骨丢失和间歇性甲状旁腺功能亢进增加骨量的机制。鉴于间歇性PTH（iPTH）治疗骨质疏松症的治疗用途，将特别关注每日一次PTH给药的骨合成代谢作用的潜在机制。
Parathyroid hormone (PTH) exerts profound effects on skeletal homeostasis through multiple cellular and molecular mechanisms. Continuous hyperparathyroidism causes net loss of bone mass, despite accelerating bone formation by osteoblasts. Intermittent treatment with PTH analogs represents the only food and Drug Administration (FDA)-approved bone anabolic osteoporosis treatment strategy. Functional PTH receptors are present on cells of the osteoblast lineage, ranging from early skeletal stem cells to matrix-embedded osteocytes. In addition, bone remodeling by osteoclasts liberates latent growth factors present within bone matrix. Here, we will provide an overview of the multiple cellular and molecular mechanisms through which PTH influences bone homeostasis. Notably, net skeletal effects of continuous versus intermittent can differ significantly. Where possible, we will highlight mechanisms through which continuous hyperparathyroidism leads to bone loss, and through which intermittent hyperparathyroidism boosts bone mass. Given the therapeutic usage of intermittent PTH (iPTH) treatment for osteoporosis, particular attention will be paid toward mechanisms underlying the bone anabolic effects of once daily PTH administration.