Osteoclasts and pain in Fibrous Dysplasia: investigating and targeting the molecular links in a transgenic mouse model (EF1α-GsαR201C mice) of human Fibrous Dysplasia
Awardee: Mara Riminucci
Institution: Sapienza University of Rome
Award Amount: $66,263
Funding Period: February 1, 2021 - January 31, 2022
Summary:
Osteoclasts are involved in the development and progression of Fibrous Dysplasia of bone (FD). Osteoclasts are skeletal cells that continuously resorb small amount of bone in a tightly regulated way and their function is necessary to allow the growth of the skeleton and its renewal. In FD lesions, osteoclasts remove bone in an uncontrolled manner and interfere with the deposition of normal mineralized bone, thus causing bone fragility. However, osteoclasts formation may not be blocked for long time in the entire skeleton. Using bone biopsies from FD patients and our mouse model of the disease, we previously identified some factors that could stimulate the abnormal formation of osteoclasts within FD lesions and other factors that could mediate their negative effects on bone formation. Therefore, in this project, we will attempt to block these factors in our FD mice in order to eliminate osteoclasts and/or their effects specifically in affected bones. Furthermore, we will start to investigate bone pain associated with the disease in the same mouse model. In particular we will investigate its mechanisms and its changes during the progression of the disease and during the proposed treatments.