Grant: Operating Grant - Priority Announcement: Neuromuscular Research

Bones and skeletal muscles constitute approximately 65% of human body weight. Bones and skeletal muscles undergo atrophy (loss of muscle and bone mass) following aging, prolonged bed rest, stroke, spinal cord injury, burns, neurodegenerative diseases, space flight, immobilization, denervation and several other debilitating conditions. It becomes obvious that skeletal muscles and bones share many biological characteristics in response to mechanical, hormonal, metabolic and pharmacologic environments. Although the biological signaling pathway called Rank/Rankl/OPG pathway is well-known to control bone mass and osteoporosis, its role in skeletal muscle has yet to be investigated. In this proposal, we use different in vivo and in vitro approaches to understand how this pathway influences muscle function under various disuses or pathological conditions. We found with the use of genetic deletion that this biological pathway plays key roles in muscle function and muscle degenerescence and also controls, to some extent, the expression of slow and fast twitch muscle fibers. This proposal is of special significance in that it may provide through the blockage of Rank/Rankl function the basic and clinical foundations for the design of novel therapeutic strategies for a wide variety of musculoskeletal and neuromusculoskeletal diseases.