Ezura Yoichi, Noda Masaki
Department of Molecular Pharmacology, Tokyo Medical and Dental University, Japan.
Clin Calcium. 2013 Feb;23(2):203-9.
PTH actions on bone are exerted through multiple pathways from G-proteins coupled to a receptor PTH1R that is expressed on osteoblastic lineage cells. Physiological action of PTH may be through increased expression of RANKL, resulting in increased bone resorption and Ca( + + ) release from bone matrix by osteoclasts. Bone anabolic action of PTH by intermittent treatment is explained by ( I ) proliferation of osteogenic precursor cells, ( II ) differentiation of osteoblasts, ( III ) inhibition of apoptosis in osteoblastic cells, and ( IV ) inhibition of canonical Wnt inhibitor secretion from osteocytes. Two of these mechanisms ( II and III ) could be secondary to increased osteoclastogenesis after induction of RANKL in osteoblastic cells. Mechanisms involved in ( I ) might be controversial depending on cellular status including differentiation stages and cell density, and thus need to be clarified by further studies.
甲状旁腺激素(PTH)对骨骼的作用是通过多种途径实现的,这些途径从与成骨细胞谱系细胞上表达的甲状旁腺激素1型受体(PTH1R)偶联的G蛋白开始。PTH的生理作用可能是通过增加核因子κB受体活化因子配体(RANKL)的表达,导致破骨细胞引起的骨吸收增加以及骨基质中钙离子(Ca++)释放。间歇性治疗时PTH的骨合成作用可通过以下几点解释:(I)成骨前体细胞的增殖,(II)成骨细胞的分化,(III)成骨细胞中细胞凋亡的抑制,以及(IV)骨细胞中经典Wnt抑制剂分泌的抑制。其中两种机制(II和III)可能继发于成骨细胞中RANKL诱导后破骨细胞生成增加。机制(I)所涉及的内容可能因细胞状态(包括分化阶段和细胞密度)而异,因此需要进一步研究加以阐明。