Muscle cells (left) fuse when treated with cGMP (right) or NO.

Nitric oxide (NO) functions at numerous points in muscle development and function. On page 233, Pisconti et al. add one more item to that list: NO stimulates myoblast fusion via cGMP signaling and follistatin. Increasing NO in vivo stimulates muscle fiber formation, which suggests a potential therapeutic approach for muscular dystrophy.

Addition of an NO-releasing compound to cultures of embryonic myoblasts or satellite cells, which function as stem cells in adult muscles, stimulated cell fusion. Conversely, addition of an inhibitor of nitric oxide synthase blocked fusion.

When the team added NO to cells but blocked production of cGMP, a known mediator of NO signaling, fusion was inhibited in a cGMP-reversible manner. Significantly, prolonged exposure of the myoblasts to a nonhydrolysable analogue of cGMP induced the formation of abnormally large muscle fibers in culture....

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