The Role of Tolloid Proteinases in bone physiology and fracture healing

Tolloid蛋白酶是一组参与细胞外基质组装的酶。人类Tolloid蛋白酶的最佳研究成员是BMP-1。已知其可促进纤维状胶原（I-III型）的成熟，裂解前体，然后自发形成胶原纤维。该项目将重点关注Tolloid蛋白酶在骨生理学和骨折愈合方面的作用，特别是酶活性的调节。对于bmp-1基因缺陷的患者，bmp-1对骨稳态的重要性变得显而易见。他们患有严重的III型成骨障碍，这可能与BMP-1的前胶原酶活性直接相关。由于I型胶原是骨中的主要结构蛋白，我们假设增加BMP-1活性将增加骨形成速率，这有利于骨折愈合。为了证实这一论点，以下几个问题需要解决：1）Tolloid蛋白酶在骨转换中有什么功能？2)骨中Tolloid蛋白酶的相互作用伙伴是什么？3)Tolloid蛋白酶如何影响骨折愈合？

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?