Spatial Genomics of Muscle-Bone interactions during Bone Regeneration

The importance of muscle-bone interactions in bone regeneration has been observed for decades. Genome-wide association studies (GWAS) suggest that muscle and bone mass/strength are co-regulated by multiple genes. Muscle is a source of osteoprogenitor cells and studies have identified muscle derived factors capable of enhancing or inhibiting osteogenesis and myogenesis following musculoskeletal injury. Notably, soft tissue damage at the fracture site is clinically recognized as a significant co-morbidity to poor bone healing outcomes. However, impairment of these interactions under age-induced osteosarcopenic conditions and their implications for regeneration have yet to be fully elucidated. Improving our understanding of the role of muscle in bone regeneration will therefore provide new opportunities to develop therapies to augment the regenerative response. Our objective in this project is thus to investigate the spatially-resolved gene expression of individual cells in the surrounding soft tissues of bone fracture sites in healthy and aged bone environments.