TGF-β and BMP signaling in osteoblast, skeletal development, and bone formation, homeostasis and disease.
TGF-β and BMP signaling in osteoblast, skeletal development, and bone formation, homeostasis and disease.
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DOI：
10.1038/boneres.2016.9
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发表时间：
2016
期刊：
影响因子：
12.7
通讯作者：
Li YP
中科院分区：
文献类型：
--
作者：
Wu M;Chen G;Li YP
转化生长因子-β（TGF-β）和骨形态发生蛋白（BMP）信号传导在胚胎骨骼发育和出生后骨稳态中具有基础作用。TGF-β和BMP作用于四聚体受体复合物，向经典的Smad依赖性信号传导途径（即TGF-β/BMP配体、受体和Smads）和非经典的Smad非依赖性信号传导途径（即p38丝裂原活化蛋白激酶/p38 MAPK）传递信号，以调节骨骼发育、骨形成和骨稳态期间的间充质干细胞分化。Smad和p38 MAPK信号通路都会聚于转录因子，例如Runx 2，以促进间充质前体细胞的成骨细胞分化和软骨细胞分化。TGF-β和BMP信号传导受多种因素控制，包括泛素-蛋白酶体系统、表观遗传因子和microRNA。TGF-β和BMP信号转导失调导致人类的许多骨疾病。小鼠中TGF-β和BMP信号相关基因的敲除或突变导致不同严重程度的骨异常，这使得能够更好地理解骨中的TGF-β/BMP信号以及成骨细胞分化和骨形成的信号网络。在TGF-β/BMP信号传导和几种关键细胞因子的信号传导途径（例如，Wnt、Hedgehog、Notch、PTHrP和FGF）之间也存在串扰，以协调骨生成、骨骼发育和骨稳态。本文综述了TGF-β/BMP信号在成骨细胞分化、软骨细胞分化、骨骼发育、软骨形成、骨形成、骨稳态以及TGF-β/BMP信号中断引起的相关人类骨疾病中的作用。
Transforming growth factor-beta (TGF-β) and bone morphogenic protein (BMP) signaling has fundamental roles in both embryonic skeletal development and postnatal bone homeostasis. TGF-βs and BMPs, acting on a tetrameric receptor complex, transduce signals to both the canonical Smad-dependent signaling pathway (that is, TGF-β/BMP ligands, receptors, and Smads) and the non-canonical-Smad-independent signaling pathway (that is, p38 mitogen-activated protein kinase/p38 MAPK) to regulate mesenchymal stem cell differentiation during skeletal development, bone formation and bone homeostasis. Both the Smad and p38 MAPK signaling pathways converge at transcription factors, for example, Runx2 to promote osteoblast differentiation and chondrocyte differentiation from mesenchymal precursor cells. TGF-β and BMP signaling is controlled by multiple factors, including the ubiquitin–proteasome system, epigenetic factors, and microRNA. Dysregulated TGF-β and BMP signaling result in a number of bone disorders in humans. Knockout or mutation of TGF-β and BMP signaling-related genes in mice leads to bone abnormalities of varying severity, which enable a better understanding of TGF-β/BMP signaling in bone and the signaling networks underlying osteoblast differentiation and bone formation. There is also crosstalk between TGF-β/BMP signaling and several critical cytokines’ signaling pathways (for example, Wnt, Hedgehog, Notch, PTHrP, and FGF) to coordinate osteogenesis, skeletal development, and bone homeostasis. This review summarizes the recent advances in our understanding of TGF-β/BMP signaling in osteoblast differentiation, chondrocyte differentiation, skeletal development, cartilage formation, bone formation, bone homeostasis, and related human bone diseases caused by the disruption of TGF-β/BMP signaling.