Stryker Biotech, Hopkinton, MA 01748, USA.
Cytokine Growth Factor Rev. 2009 Oct-Dec;20(5-6):501-7. doi: 10.1016/j.cytogfr.2009.10.001. Epub 2009 Nov 11.
Bone morphogenetic proteins (BMPs) are growth factors belonging to the TGF beta super family. To date, more than twenty human BMPs have been identified. Of these, BMP-2 and BMP-7 (also known as osteogenic protein 1 or OP-1) are the only BMPs used clinically. Recombinant forms of both proteins are currently being implanted surgically to induce spinal fusion and to treat long bone non-union fractures. However, in both indications, large quantities of recombinant proteins are needed to induce new bone formation. This translates to higher costs and potential safety risks. Various genetic engineering approaches are being considered to produce second generation BMPs with improved safety and efficacy profiles. Modified BMPs with one or more of the following characteristics are being considered: (i) improved binding affinity to specific target cell surface BMP receptors, (ii) decreased sensitivity to natural BMP inhibitors, (iii) better immunogenicity profile, and (iv) increased solubility and stability, to cite a few. This review summarizes the progress made so far in this field and gives a perspective on what the next generation BMPs could look like.
骨形态发生蛋白（BMPs）属于 TGF-β超家族的生长因子。迄今为止，已经鉴定出二十多种人类 BMP。其中，BMP-2 和 BMP-7（也称为骨形成蛋白 1 或 OP-1）是唯一在临床上使用的 BMP。这两种蛋白质的重组形式目前正在通过手术植入以诱导脊柱融合和治疗长骨骨不连骨折。然而，在这两种适应症中，都需要大量的重组蛋白来诱导新骨形成。这意味着更高的成本和潜在的安全风险。正在考虑各种基因工程方法来生产具有改进的安全性和疗效特征的第二代 BMP。正在考虑具有以下一种或多种特征的改良 BMP：（i）与特定靶细胞表面 BMP 受体的结合亲和力提高，（ii）对天然 BMP 抑制剂的敏感性降低，（iii）更好的免疫原性特征，和（iv）增加的溶解度和稳定性等。本文综述了该领域迄今为止取得的进展，并对下一代 BMP 可能的样子进行了展望。
