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BMPs:从骨到全身形态发生蛋白。

BMPs: from bone to body morphogenetic proteins.

机构信息

1Institute of Chemistry and Biochemistry, Freie Universitaet Berlin, Berlin, Germany.

出版信息

Sci Signal. 2010 Feb 2;3(107):mr1. doi: 10.1126/scisignal.3107mr1.

Abstract

The family of bone morphogenetic proteins (BMPs) comprises approximately 30 secreted cytokines that signal through transmembrane serine/threonine kinase receptors. The BMP signaling pathways are fine-tuned on multiple levels: Extracellular antagonists modify ligand activity; several co-receptors enhance or inhibit downstream signaling events through multiple mechanisms; and intracellular molecules further regulate the signaling outcome and mediate crosstalk with other pathways. BMPs affect structures and processes throughout the entire body, ranging from embryonic patterning and development through stem cells and their niches, to tissue homeostasis and regeneration. This comprehensive involvement in various tissues had not been expected by Marshall Urist, who initially discovered the ability of an unknown factor in bone to induce bone growth in muscle and subsequently suggested the name "bone morphogenetic protein." Today, recombinant BMPs are used in clinical practice for the treatment of bone and kidney disorders, and new genetically modified BMPs are emerging as promising tools in regenerative medicine and tissue engineering. Clearly, the functions of BMPs within the body are more versatile than initially suspected. To discuss modern trends in BMP signaling, leaders in the field met for the First International BMP Workshop in Berlin in September 2009. Here, we summarize new insights on the roles of BMPs in various tissues and highlight recent findings in cell, structural, and developmental biology as well as the therapeutic potential of BMPs. Finally, we conclude that BMPs today deserve to be called body morphogenetic proteins.

摘要

骨形态发生蛋白(BMPs)家族大约包含 30 种分泌型细胞因子,通过跨膜丝氨酸/苏氨酸激酶受体发挥信号转导作用。BMP 信号通路在多个层面上进行精细调控:细胞外拮抗剂调节配体活性;几种共受体通过多种机制增强或抑制下游信号事件;细胞内分子进一步调节信号转导结果,并介导与其他通路的串扰。BMPs 影响全身的结构和过程,从胚胎模式形成和发育到干细胞及其龛位,再到组织内稳态和再生。马歇尔·乌里斯特(Marshall Urist)最初发现了一种未知因子在骨骼中诱导肌肉生长的能力,并随后提出了“骨形态发生蛋白”的名称,他最初并没有预料到 BMP 会在如此广泛的组织中发挥作用。如今,重组 BMP 已在临床实践中用于治疗骨骼和肾脏疾病,新型基因修饰的 BMP 作为再生医学和组织工程的有前途的工具正在不断涌现。显然,BMP 在体内的功能比最初预期的更为多样化。为了讨论 BMP 信号转导的现代趋势,该领域的领导者于 2009 年 9 月在柏林举行了第一届国际 BMP 研讨会。在这里,我们总结了 BMP 在各种组织中的作用的新见解,并强调了细胞、结构和发育生物学以及 BMP 治疗潜力方面的最新发现。最后,我们得出结论,BMP 现在当之无愧地被称为身体形态发生蛋白。

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