TGF-β/BMP signaling and other molecular events: regulation of osteoblastogenesis and bone formation.
TGF-β/BMP signaling and other molecular events: regulation of osteoblastogenesis and bone formation.
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DOI：
10.1038/boneres.2015.5
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发表时间：
2015
期刊：
影响因子：
12.7
通讯作者：
Asaduzzaman, Sikder M.
中科院分区：
文献类型：
--
作者：
Rahman, Md Shaifur;Akhtar, Naznin;Jamil, Hossen Mohammad;Banik, Rajat Suvra;Asaduzzaman, Sikder M.
转化生长因子-β（Transforming growth factor-beta，TGF-β）/骨形态发生蛋白（bone morphogenetic protein，BMP）通过激活受体丝氨酸/苏氨酸激酶（serine/threonine kinases）在骨器官发生的调控中发挥重要作用。TGF-β/BMP活性的扰动几乎总是与多种临床结果相关，即，骨骼、骨骼外异常、自身免疫、癌症和心血管疾病。TGF-β（I/II）或BMP受体的磷酸化激活细胞内下游Smads，其为TGF-β/BMP信号的转换器。这种信号传导受多种因子和途径调节，包括转录因子Runx 2。骨骼发育和骨形成中的信号网络极其复杂，并且具有高度的时空特异性。当TGF-β/BMP与MAPK、Wnt、Hedgehog（Hh）、Notch、Akt/mTOR和miRNA等通路相互作用以调节BMP诱导的信号传导在骨动力学中的作用时，观察到相加、正、负或协同效应。越来越多的证据表明Runx 2是关键的整合者，而Hh是可能的调节剂，miRNA是调节剂，β-连环蛋白是广泛的细胞内网络中的介体/调节剂。本文综述了BMP信号的激活及其与其他调控成分和途径的相互作用，重点介绍了TGF-β/BMP功能和调控的分子机制，有助于理解骨组织动力学的复杂性。
Transforming growth factor-beta (TGF-β)/bone morphogenetic protein (BMP) plays a fundamental role in the regulation of bone organogenesis through the activation of receptor serine/threonine kinases. Perturbations of TGF-β/BMP activity are almost invariably linked to a wide variety of clinical outcomes, i.e., skeletal, extra skeletal anomalies, autoimmune, cancer, and cardiovascular diseases. Phosphorylation of TGF-β (I/II) or BMP receptors activates intracellular downstream Smads, the transducer of TGF-β/BMP signals. This signaling is modulated by various factors and pathways, including transcription factor Runx2. The signaling network in skeletal development and bone formation is overwhelmingly complex and highly time and space specific. Additive, positive, negative, or synergistic effects are observed when TGF-β/BMP interacts with the pathways of MAPK, Wnt, Hedgehog (Hh), Notch, Akt/mTOR, and miRNA to regulate the effects of BMP-induced signaling in bone dynamics. Accumulating evidence indicates that Runx2 is the key integrator, whereas Hh is a possible modulator, miRNAs are regulators, and β-catenin is a mediator/regulator within the extensive intracellular network. This review focuses on the activation of BMP signaling and interaction with other regulatory components and pathways highlighting the molecular mechanisms regarding TGF-β/BMP function and regulation that could allow understanding the complexity of bone tissue dynamics.
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影响因子：
5.1
作者：
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DOI：
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影响因子：
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DOI：
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发表时间：
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期刊：
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影响因子：
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