The Role of Tolloid Proteinases in bone physiology and fracture healing

• Applicant: Dr. Daniel Kronenberg
• Subject Area: Orthopaedics, Traumatology, Reconstructive Surgery ; Animal Physiology and Biochemistry
• Term: from 2014 to 2018
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 259960453

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?

• DFG Programme: Research Grants
• Participating Person: Professor Dr. Richard Stange