Project Grant K99AR088542

The National Institutes of Health National Institute of Arthritis and Musculoskeletal and Skin Diseases awarded Duke University $124,875 on September 1, 2026, under the Arthritis, Musculoskeletal and Skin Diseases Research program (CFDA 93.846) to investigate muscle-to-bone communication during fracture repair and musculoskeletal regeneration.

The research identifies pro-regenerative signals from injured muscle that orchestrate repair of both bone and muscle tissue. Preliminary findings demonstrate that bone injury triggers a 24-fold increase in CX3CL1 gene expression in muscle, with endothelial cells as the primary source. The work reveals that osteoblast progenitors respond to muscle-derived CX3CL1 through receptor upregulation and show robust bone-forming capacity when exposed to recombinant CX3CL1 in vitro. The research addresses clinical significance: patients with fractures complicated by muscle defects experience poor recovery, and fracture outcomes worsen in osteosarcopenia—the coexistence of osteoporosis and muscle weakness—compared to osteoporosis alone. Current therapies target bone and muscle separately, leaving patients without effective treatment options. Identifying key muscle-derived signals may provide a foundation for dual therapies promoting simultaneous bone and muscle regeneration.

Work is performed in Durham, North Carolina, with the period of performance running through August 31, 2028. This is a Project Grant, the assistance type used for discrete, time-limited research investigations.