5 The Bone Morphogenetic Proteins
5 The Bone Morphogenetic Proteins
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5 骨形态发生蛋白
DOI：
10.1101/087969752.50.121
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发表时间：
2008
期刊：
影响因子：
--
通讯作者：
K. Miyazono
中科院分区：
文献类型：
--
作者：
T. Katagiri;T. Suda;K. Miyazono
骨形态发生蛋白 (BMP) 通过调节多种细胞的增殖、分化和凋亡，在骨骼发育中发挥关键作用。 BMP 的分子克隆和与其同源的分子的鉴定揭示了 BMP 在脊椎动物和无脊椎动物（包括果蝇和线虫）中的新功能。在本章中，我们描述了 BMP 的生化特性和生物活性；我们特别关注 BMP 诱导的细胞分化。尽管现在已知BMP在脊椎动物和无脊椎动物中具有多功能因子，但它们最初是在1965年被发现并鉴定为骨基质中的骨诱导活性。Marshall R. Urist (1965)首先通过用盐酸处理骨来制备脱矿骨，然后将脱矿骨植入肌肉组织中。移植几周后，他发现肌肉组织中已经异位形成了新的软骨和带有骨髓的骨组织（Urist 1965）。这些发现清楚地表明脱矿骨基质含有能够诱导肌肉组织中骨形成细胞分化的未知生物活性物质。这种异位骨诱导活性随后被命名为“骨形态发生蛋白”，因为它在胰蛋白酶消化后消失（Urist 和 Strates 1971）。然而，在 Urist 最初发现之后的 20 多年里，由于从骨基质中分离 BMP 存在困难，所有分离和鉴定 BMP 的尝试均未成功。 BMP 活性不溶于水，可以用蛋白质变性剂从脱矿骨基质中提取（Urist 和 Strates 1971；Sampath 和 Reddi 1981；Yoshikawa 等...
Bone morphogenetic proteins (BMPs) have critical roles in skeletal development by regulating the proliferation, differentiation, and apoptosis of many types of cells. Molecular cloning of BMPs and identification of molecules homologous to them have shed light on the novel functions of BMPs in vertebrates as well as in invertebrates, including Drosophila and nematodes. In this chapter, we describe biochemical properties and biological activities of BMPs; we focus, in particular, on the cell differentiation induced by BMPs. Although BMPs are now known to be multifunctional factors in vertebrates and invertebrates, they were originally discovered and identified as a bone-inducing activity in bone matrix in 1965. Marshall R. Urist (1965) first prepared demineralized bone by treating bone with hydrochloric acid and then implanting the demineralized bone in muscular tissues. A few weeks after transplantation, he found that new cartilage and bone tissues with bone marrow had been ectopically formed in muscular tissue (Urist 1965). These findings clearly indicated that the demineralized bone matrix contained unknown bioactive substance(s) capable of inducing differentiation of bone-forming cells in muscular tissues. This ectopic bone-inducing activity was subsequently named “bone morphogenetic protein,” because it disappeared after trypsin digestion (Urist and Strates 1971). However, all attempts to isolate and identify BMP were unsuccessful for more than 20 years after Urist’s original findings because of the difficulty in isolating BMP from bone matrix. BMP activity was water insoluble and could be extracted from demineralized bone matrix with protein denaturants (Urist and Strates 1971; Sampath and Reddi 1981; Yoshikawa et...