Assessment of role of RANKL and its inhibition on muscle mass and function.

The role of inflammation in musculoskeletal dysfunction is increasingly recognised, whether driven by concurrent age-related disease or directly by accumulation of senescence-associated, secretory phenotype cells (SASPs). Many inflammatory mediators have been implicated in these processes, including the fundamental RANKL-RANK-NFKB2 pathway. A potent inhibitor of RANKL, namely denosumab (a fully humanized monoclonal antibody) is currently widely used in the field of osteoporosis. The projects aims to extend knowledge of role of RANKL on muscle in pre-clinical models; determine changes in muscle mass, strength and performance in patients undergoing short and long-term exposure to denosumab.

This proposal will provide a broad range of project-specific and transferable research skills. At least one placement will be incorporated into the student’s PhD programme, namely to the Department of Musculoskeletal Biology in Liverpool, where training in muscle analysis will be undertaken. In a further placement, s/he will gain knowledge of the epigenetic techniques including sample collection, preparation, analysis and interpretation.