Establishment of the premises for using the pro-form of bone morphogenetic protein (BMP-2) as a therapeutic tool

建立使用骨形态发生蛋白（BMP-2）原体作为治疗工具的场所

• 批准号: 37843318
• 负责人: Professorin Dr. Elisabeth Schwarz
• 金额: --
• 依托单位: Abteilung Technische Biochemie (aufgelöst)
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2007
• 资助国家: 德国
• 起止时间: 2006-12-31 至 2010-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/37843318?language=en
• 关键词: Establishment; premises; using; pro; form

Bone morphogenetic protein (BMP-2) is in clinical use since 2002. Clinical indications are mainly slow healing fractures. Recently, the administration of BMP-2 has been reported to be accompanied by adverse side effects. Since in our studies significantly lower doses of BMP-2 than those applied in the clinic had induced ectopic bone formation, the side effects may be due to insufficient doses adjustment. For the related transforming growth factor-ß (TGF-ß), a latency conferring role of the pro-peptide has been demonstrated. Our own data indirectly suggest that the pro-peptide of BMP-2 may retard the activity of the mature growth factor. Thus, proBMP-2 may be a late acting therapeutic protein by which overdoses effects may be intrinsically counteracted by the pro-peptide. The objective of the proposal is testing the premises for administration of proBMP-2 as a novel, delayed acting drug for bone regeneration. The following subtopics will be dealt with: Optimization of recombinant production and refolding of authentic proBMP-2, analysis of the effect of carrier materials (for in vivo delivery) and spin labels (for in vivo monitoring) on structure and function of the protein, determination of growth factor release from the carrier material and determination of the biological responses elicited by proBMP-2.

自2002年以来，骨形态发生蛋白（BMP-2）从事临床用途。临床适应症主要是缓慢的愈合因子。最近，据报道，BMP-2的给药伴随着不利的副作用。由于在我们的研究中，BMP-2的剂量明显低于诊所中所诱导的生态骨形成，因此副作用可能是由于调整剂量不足所致。对于相关的转化生长因子-β（TGF-ß），已经证明了促肽的潜伏期赋予作用。我们自己的数据间接表明，BMP-2的促肽可能会阻碍成熟生长因子的活性。这可能是probMP-2可能是晚期作用的治疗蛋白，通过该蛋白可以通过促肽内在抵消过量作用。该提案的目的是测试用于给药的前提，作为一种新型，延迟的作用药物，用于骨骼再生。将处理以下子主题：优化重组生产和重新折叠真实的ProbMP-2，载体材料的影响（用于体内输送）和自旋标签（用于体内监测）对蛋白质结构和功能的自旋标签（用于体内监测），确定载载材料的生长因子释放的生长因子释放和生物学响应的确定，并确定生物学响应的pociDe pociped pocipited pericited pericited pericited。