Osteogenic Peptides in Bone Regeneration
Osteogenic Peptides in Bone Regeneration
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DOI：
10.2174/1381612811319190006
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发表时间：
2013-06-01
影响因子：
3.1
通讯作者：
Jabbari, Esmaiel
中科院分区：
文献类型：
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作者：
Jabbari, Esmaiel
由于它们的半衰期短和从再生部位扩散，用于再生医学的成骨蛋白需要高剂量，导致不希望的副作用。一种令人兴奋的方法是利用来自骨细胞外基质（ECM）的可溶性和不溶性组分的活性结构域的肽来启动骨生成、血管生成、矿化和骨形成的级联反应。衍生自骨形态发生蛋白的成骨肽、整合素结合肽和肝素结合肽、胶原衍生肽、衍生自骨唾液蛋白和釉基质蛋白的肽、血管收缩肽、衍生自参与染色质结构的组蛋白的肽和衍生自人凝血酶的受体结合结构域的肽、消除肿瘤坏死因子-α表达的肽、和神经肽被发现。在这项工作中，成骨肽的合成代谢作用，特别是相对于细胞粘附，分化和矿化进行了讨论。当通过缀合或接枝固定在基质中时，这些肽在小动物模型中在体外和体内显示出显著更高的生物活性，这很可能是由于肽的移动性及其从再生位点扩散开。成骨肽和整合素结合肽的组合协同增强细胞粘附和矿化。用成骨肽对骨科植入物进行功能化可以改善细胞粘附、矿化以及植入物与周围组织的整体整合，这反过来又减少了植入物松动和失效。在骨科应用中使用成骨肽作为替代生长因子取决于未来在灵长类动物和人类中评估这些肽的体内研究。
Due to their short half-life and diffusion away from the site of regeneration, osteogenic proteins, used in regenerative medicine, require high doses leading to undesirable side effects. An exciting approach is to utilize peptides derived from the active domains of soluble and insoluble components of the bone extracellular matrix (ECM) to initiate the cascade of osteogenesis, vasculogenesis, mineralization, and bone formation. Osteogenic peptides derived from bone morphogenetic proteins, integrin-binding and heparin-binding peptides, collagen-derived peptides, peptides derived from bone sialoprotein and enamel matrix proteins, vasoconstrictive peptides, peptides derived from the histone proteins involved in the structure of chromatin and those derived from receptor-binding domain of human thrombin, peptides that abolish the expression of tumor necrosis factor-alpha, and neuropeptides have been discovered. In this work, anabolic effects of osteogenic peptides in particular with respect to cell adhesion, differentiation, and mineralization are discussed. These peptides show significantly higher biological activity in vitro and in vivo, in small animal models, when immobilized in a matrix by conjugation or grafting, most likely due to the peptide mobility and its diffusion away from the site of regeneration. Combination of osteogenic and integrin-binding peptides synergistically enhances cell adhesion and mineralization. Functionalization of orthopedic implants with osteogenic peptides can improve cell adhesion, mineralization, and overall integration of the implant with the surrounding tissue, which in turn reduces implant loosening and failure. The use of osteogenic peptides as an alternative growth factor in orthopedic applications rests on future in vivo studies that evaluate these peptides in primates and humans.