BMP binding peptide: a BMP-2 enhancing factor deduced from the sequence of native bovine bone morphogenetic protein/non-collagenous protein
BMP binding peptide: a BMP-2 enhancing factor deduced from the sequence of native bovine bone morphogenetic protein/non-collagenous protein
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DOI：
10.1016/j.orthres.2004.05.001
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发表时间：
2005-01-01
影响因子：
2.8
通讯作者：
Murray, SS
中科院分区：
文献类型：
--
作者：
Behnam, K;Phillips, ML;Murray, SS
四十年前，Marshall Urist 描述了一种部分纯化的脱矿骨基质提取物，可诱导异位骨的形成。这种物质，即骨形成蛋白/非胶原蛋白 (BMP\NCP)，从未纯化至均质，但其他研究人员使用类似的起始材料克隆了许多重组 B-MP。乌里斯特认识到他的材料可能含有其他人克隆的 BMP，但始终认为它含有另一种更有效的骨诱导材料，其物理和化学性质与已知的 BMP 显着不同。我们使用 Urist 的方案分离出具有 Urist 的“BMP”化学和物理特性的蛋白质。它是骨基质蛋白 SPP-24 的 18.5 kD 片段。该片段包含 SPP-24 的半胱氨酸蛋白酶抑制剂样结构域。我们找到了一个 19 个氨基酸的区域，该区域与胎球蛋白的 TGF-β/BMP 结合区域相似。蛋白酶抑制剂半胱氨酸蛋白酶抑制剂家族的成员。沿着该序列生成了一种环肽，我们称之为 BMP 结合肽 (BBP)。该肽以 3 x 10(-5) M 的 K-D 强烈结合 rhBMP-2。当单独植入小鼠肌肉时，该肽经常诱导营养不良性钙化。当植入rhBMP-2时。该肽增强了重组分子的成骨活性。我们假设 Urist 的“BMP”是 SPP-24 的片段，它通过与骨形态发生蛋白结合来影响骨诱导。 BBP 可能在临床上有用，因为它对其他骨诱导物质有影响。由 Elsevier Ltd. 代表骨科研究协会出版。
Forty years ago, Marshall Urist described a partially purified extract of dermineralized bone matrix which induced the formation of ectopic bone. This substance, bone rnorphogenetic protein/non-collagenous protein (BMP\NCP), was never purified to homogeneity but other investigators used similar starting materials to clone a number of recombinant B-MPs. Urist recognized that his material probably contained the BMPs which had been cloned by others but always contended that it contained another, more potent, bone inducing material which differed significantly in its physical and chemical properties from the known BMPs. We have used Urist's protocol to isolate a protein that has the chemical and physical properties of Urist's "BMP". It is an 18.5 kD fragment of the bone matrix protein, SPP-24. This fragment contains the cystatin-like domain of SPP-24. We have located a 19 amino acid region which is similar to the TGF-beta/BMP-binding region of fetuin. a member of the cystatin family of protease inhibitors. A cyclic peptide, which we call BMP binding peptide (BBP) was generated rising this sequence. The peptide avidly bound rhBMP-2 with a K-D of 3 x 10(-5) M. When implanted alone in mouse muscle, the peptide frequently induced dystrophic calcification. When implanted with rhBMP-2. the peptide enhanced the osteogenic activity of the recombinant molecule. We hypothesize that Urist's "BMP" was a fragment of SPP-24 which influenced bone induction by binding to bone morphogenetic proteins. BBP may be clinically useful because of its effects on other bone-inducing Substances. Published by Elsevier Ltd. on behalf of Orthopaedic Research society.