The Role of Tolloid Proteinases in bone physiology and fracture healing

类Tolloid蛋白水解酶是一组参与细胞外基质组装的酶。人类Tolloid蛋白水解酶中研究最多的成员是BMP-1。众所周知，它能促进纤维状胶原蛋白(I-III型)的成熟，裂解ProForm，然后自发形成胶原纤维。本项目将侧重于Tolloid蛋白酶在骨生理学和骨折愈合中的作用，特别是关于酶活性的调节。当考虑到BMP-1基因缺陷的患者时，BMP1对骨稳态的主要重要性变得显而易见。他们患有严重的III型成骨不全，这可能与BMP-1的前胶原酶活性直接相关。由于I型胶原是骨骼中的主要结构蛋白，我们推测增加BMP-1的活性会增加骨形成速度，从而有利于骨折的愈合。为了证实这一观点，需要解决以下问题：1)Tolloid蛋白在骨转换中有什么作用？2)Tolloid蛋白在骨中的相互作用伙伴是什么？3)Tolloid蛋白是如何影响骨折愈合的？

Tolloid proteinases are a group of enzymes which are involved in the assembly of the extracellular matrix. The best studied member of human Tolloid protenases is BMP-1. It is known for promoting the maturation of fibrillar collagens (type I-III), cleaving the proform which afterwards spontaneously forms collagen fibrils. This project will focus onto the role of Tolloid proteinases in the context of bone physiology and fracture healing, with special regard to regulation of enzyme activity. The major importance of BMP1 for bone homeostasis becomes obvious when regarding patients with a defective bmp-1 gene. They suffer from a severe form of type III osteogenesis imperfectat which could be directly linked to the procollagenase activity of BMP-1. Since Collagen type I is the major structural protein in bone, we hypothesize that increasing the BMP-1 activity will increase the bone formation rate which is beneficial for fracture healing. To corroborate this thesis following topics should be addressed:1) What functions have the Tolloid proteinases in bone turnover?2) What are the interaction partners of Tolloid proteinases in bone?3) How do the Tolloid proteinases affect the fracture healing?