Institute of Genetics, Life Science College, Zhejiang University, 388 Yuhang Road, Hangzhou 310058, China.
Int J Biol Sci. 2012;8(2):272-88. doi: 10.7150/ijbs.2929. Epub 2012 Jan 21.
Transforming growth factor-beta (TGF-β)/bone morphogenic protein (BMP) signaling is involved in a vast majority of cellular processes and is fundamentally important throughout life. TGF-β/BMPs have widely recognized roles in bone formation during mammalian development and exhibit versatile regulatory functions in the body. Signaling transduction by TGF-β/BMPs is specifically through both canonical Smad-dependent pathways (TGF-β/BMP ligands, receptors and Smads) and non-canonical Smad-independent signaling pathway (e.g. p38 mitogen-activated protein kinase pathway, MAPK). Following TGF-β/BMP induction, both the Smad and p38 MAPK pathways converge at the Runx2 gene to control mesenchymal precursor cell differentiation. The coordinated activity of Runx2 and TGF-β/BMP-activated Smads is critical for formation of the skeleton. Recent advances in molecular and genetic studies using gene targeting in mice enable a better understanding of TGF-β/BMP signaling in bone and in the signaling networks underlying osteoblast differentiation and bone formation. This review summarizes the recent advances in our understanding of TGF-β/BMP signaling in bone from studies of genetic mouse models and human diseases caused by the disruption of TGF-β/BMP signaling. This review also highlights the different modes of cross-talk between TGF-β/BMP signaling and the signaling pathways of MAPK, Wnt, Hedgehog, Notch, and FGF in osteoblast differentiation and bone formation.
转化生长因子-β（TGF-β）/骨形态发生蛋白（BMP）信号通路参与了绝大多数细胞过程，在整个生命过程中都具有重要的基础作用。TGF-β/BMP 在哺乳动物发育过程中的骨形成中具有广泛的作用，并在体内具有多种调节功能。TGF-β/BMP 的信号转导是通过经典的 Smad 依赖性途径（TGF-β/BMP 配体、受体和 Smads）和非经典的 Smad 非依赖性信号通路（如 p38 丝裂原活化蛋白激酶途径，MAPK）来特异性实现的。在 TGF-β/BMP 诱导后，Smad 和 p38 MAPK 途径都集中在 Runx2 基因上，以控制间充质前体细胞的分化。Runx2 和 TGF-β/BMP 激活的 Smads 的协调活动对于骨骼的形成至关重要。利用基因靶向在小鼠中进行的分子和遗传研究的最新进展，使我们能够更好地理解 TGF-β/BMP 信号在骨骼中的作用，以及在成骨细胞分化和骨形成的信号网络中。本综述总结了从遗传小鼠模型和 TGF-β/BMP 信号中断引起的人类疾病研究中，我们对 TGF-β/BMP 信号在骨骼中的作用的最新认识。本综述还强调了 TGF-β/BMP 信号与 MAPK、Wnt、Hedgehog、Notch 和 FGF 信号通路在成骨细胞分化和骨形成中的不同交叉对话模式。
