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Disease mechanisms and therapeutic interventions in non-classical osteogenesis imperfecta

Subject Area Orthopaedics, Traumatology, Reconstructive Surgery
Term since 2018
Project identifier Deutsche Forschungsgemeinschaft (DFG) - Project number 384170921
 
Classical Osteogenesis imperfecta (OI) is caused by mutations in collagen I encoding genes that eventually lead to a reduced quality and/or quantity of collagen I in the extracellular matrix (ECM). The non-classical OI forms described so far have been associated with genes and proteins that are essential for the synthesis, intracellular trafficking and secretion of collagen I. Recently, we have identified KDELR2 as a novel OI-causing gene. In primary dermal fibroblasts isolated from OI patients, we described a molecular mechanism in which the collagen chaperone Hsp47 plays a crucial role. The clinical and genetic analyses of additional patients will be continued and has already led to the identification of the gene TAPT1. We ultimately aim to unravel the underlying disease mechanisms at the molecular and cellular levels in patient cells and mouse models. Thus, our study will not only provide important insights into fundamental processes in protein secretion and ECM homeostasis, but could also enable the development of novel therapeutic approaches individually tailored to the disease mechanism.
DFG Programme Research Units
 
 

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