Halloran Daniel, Durbano Hilary W, Nohe Anja
Department of Biological Sciences, University of Delaware, Newark, DE 19716, USA.
J Dev Biol. 2020 Sep 13;8(3):19. doi: 10.3390/jdb8030019.
Bone morphogenetic proteins (BMPs) are multi-functional growth factors belonging to the Transforming Growth Factor-Beta (TGF-β) superfamily. These proteins are essential to many developmental processes, including cardiogenesis, neurogenesis, and osteogenesis. Specifically, within the BMP family, Bone Morphogenetic Protein-2 (BMP-2) was the first BMP to be characterized and has been well-studied. BMP-2 has important roles during embryonic development, as well as bone remodeling and homeostasis in adulthood. Some of its specific functions include digit formation and activating osteogenic genes, such as (). Because of its diverse functions and osteogenic potential, the Food and Drug Administration (FDA) approved usage of recombinant human BMP-2 (rhBMP-2) during spinal fusion surgery, tibial shaft repair, and maxillary sinus reconstructive surgery. However, shortly after initial injections of rhBMP-2, several adverse complications were reported, and alternative therapeutics have been developed to limit these side-effects. As the clinical application of BMP-2 is largely implicated in bone, we focus primarily on its role in bone. However, we also describe briefly the role of BMP-2 in development. We then focus on the structure of BMP-2, its activation and regulation signaling pathways, BMP-2 clinical applications, and limitations of using BMP-2 as a therapeutic. Further, this review explores other potential treatments that may be useful in treating bone disorders.
骨形态发生蛋白(BMPs)是属于转化生长因子-β(TGF-β)超家族的多功能生长因子。这些蛋白质对许多发育过程至关重要,包括心脏发生、神经发生和成骨作用。具体而言,在BMP家族中,骨形态发生蛋白-2(BMP-2)是第一个被鉴定且研究充分的BMP。BMP-2在胚胎发育以及成年期的骨重塑和内环境稳定中发挥重要作用。其一些特定功能包括指(趾)形成和激活成骨基因,如()。由于其多样的功能和成骨潜力,美国食品药品监督管理局(FDA)批准在脊柱融合手术、胫骨干修复和上颌窦重建手术中使用重组人BMP-2(rhBMP-2)。然而,在首次注射rhBMP-2后不久,就有几例不良并发症的报道,并且已经开发出替代疗法来限制这些副作用。由于BMP-2的临床应用主要与骨相关,我们主要关注其在骨中的作用。不过,我们也简要描述了BMP-2在发育中的作用。然后我们聚焦于BMP-2的结构、其激活和调节信号通路、BMP-2的临床应用以及将BMP-2用作治疗手段的局限性。此外,本综述探讨了其他可能对治疗骨疾病有用的潜在疗法。