Localized chondro-ossification underlies joint dysfunction and motor deficits in the Fkbp10 mouse model of osteogenesis imperfecta

Significance Osteogenesis imperfecta (OI), also known as brittle bone disease, commonly features low bone mass and frequent fractures. We and others have previously identified mutations that cause joint deformities in OI patients. However, mechanisms responsible for joint pathologies in OI are poorly understood. Here, we have established a mouse model of OI joint dysfunction that is caused by mutations in Fkbp10 . Our mouse model recapitulates key features of FKBP10 OI patients, including reduced collagen cross-linking and joint deformities. In addition, we found that inflammation and altered matrix signaling is associated with joint abnormalities in Fkbp10 mutant animals. Overall, our work provides a valuable model that can be used to identify novel therapies to treat joint dysfunction in OI and OI-related diseases.