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. A similar effect was not observed with extended exposure to an NO donor.
RT-PCR analysis of NO-treated myoblasts showed that follistatin, a protein known to trigger myoblast fusion, was up-regulated relative to untreated cells. Another fusion-promoting protein, insulin growth factor-1 (IGF-1) was not increased.
The results suggest that NO donors may be valuable as therapies for muscular dystrophy. Preliminary testing in animal models supports that idea.
Note: The paper highlighted in this In This Issue was retracted on January 22, 2013.