间断PTH处理调节骨稳态的分子机制

The molecular mechanism of bone homeostasis regulated by intermittent PTH treatment

骨稳态是成骨细胞介导的骨形成和破骨细胞负责的骨吸收之间的动态平衡。甲状旁腺激素(parathyroid hormone,PTH)间断处理主要通过增加成骨细胞的数量和活性促进骨形成。体内外研究表明PTH促进骨合成的细胞学机制包括:促进前成骨细胞分化为成骨细胞;抑制脂肪细胞的生成;使骨衬细胞重新激活以及抑制成骨细胞的凋亡。PTH与细胞膜上受体PTHR1(parathyroid hormonereceptor 1)结合,通过cAMP/PKA和PLC/PKC传递下游信号。间断PTH促骨合成作用的分子机制虽不完全清楚,但目前已有不少PTH骨合成信号介导分子的研究报道,如IGF1,TGFβ,Wnt以及FGF等,本文就其研究进展作一综述。

Bone homeostasis is a dynamic equilibrium which is associated with bone formation mediated by osteoblasts and bone resorption mediated by osteoclasts. Intermittent PTH treatment increase bone formation by enhancing osteoblast number and activity. Studies in vivo and in vitro have shown that the cellular mechanisms of anabolic effects of PTH include： recruitment of osteoblast precursors, attenuation of adipogenesis, activation of bone lining cells, and inhibition of osteoblast apoptosis. PTH binds to PTHR1 and then activates downstream cAMP/PKA and PLC/PKC signaling. The underlying molecular mechanisms of PTH anabolic effect are incompletely understood, however, there are increasing reports about molecular participants in mediating PTH bone anabolic action, such as IGF1, TGFβ, Wnt, and FGF. This paper reviews the recent advances.