Specific amino acids from the broad C-terminal region of BMP-2 are crucial for osteogenesis.

来自 BMP - 2 的宽 C 末端区域的特定氨基酸对于成骨至关重要。

• 发表时间: Jun 2021
• 来源期刊: Bone Rep
• DOI: 10.1016/j.bonr.2021.101092
• PMID: 34026953
• 文章类型: Journal Article
• 作者列表: Karoulias SZ,Pitou M,Papi R,Lamprou P,Choli-Papadopoulou T

关键词: AP, Alkaline Phosphatase; Alizarin Red; Alkaline phosphatase; B2M, beta-2 microglobulin; BMP, Bone Morphogenetic Protein; BMPR, Bone Morphogenetic Protein receptor; ERK, Extracellular signal-Regulated Kinase; MAPK, Mitogen-Activated Protein Kinase; Osteo-implants; Osteogenesis; Osteogenetic peptides; TGF, Transforming Growth Factor

Abstract

The shortest functional domains of growth factor Bone Morphogenetic Protein 2 (BMP-2) that are dynamical implicated in osteogenesis have been investigated and well characterized. In particular, the broad C-terminal region expanding from Val63 to Arg114 as well as its shorter sequence 86-AISMLYLDEN-95 exhibited the highest osteogenic ability for regeneration and reconstruction of bone tissue. In addition, the amino acids Ser88 and Leu90 have been identified as crucial for receptor binding and osteogenic efficacy. Furthermore, the above-mentioned domains in contrary to full length BMP-2 protein signal mainly through the Smad pathway as it is evidenced by phosphorylation decrease of Extracellular-signal-Regulated Kinase (ERK1/2). Taking together, our results are significant for clinical applications regarding the generation of biomaterials and healing of orthopedic fractures.

摘要

已经研究并充分表征了与成骨发生动态相关的生长因子骨形态发生蛋白2（BMP-2）的最短功能域。特别是,从Val63扩展到Arg114的宽C端区域及其较短的序列86-AISMLYLDEN-95表现出最高的成骨能力，可用于骨组织的再生和重建。此外,氨基酸Ser88和Leu90已被鉴定为对受体结合和成骨功效至关重要。此外，与全长BMP-2蛋白信号信号相反,上述结构域主要通过Smad途径,如细胞外信号调节激酶(ERK1/2)的磷酸化减少所证明。一起,我们的结果对于生物材料的产生和骨科骨折的愈合方面的临床应用具有重要意义.