| First Author | Dufresne SS | Year | 2017 |
| Journal | Am J Pathol | Volume | 187 |
| Issue | 3 | Pages | 498-504 |
| PubMed ID | 28041995 | Mgi Jnum | J:240178 |
| Mgi Id | MGI:5882624 | Doi | 10.1016/j.ajpath.2016.11.006 |
| Citation | Dufresne SS, et al. (2017) Osteoprotegerin and beta2-Agonists Mitigate Muscular Dystrophy in Slow- and Fast-Twitch Skeletal Muscles. Am J Pathol 187(3):498-504 |
| abstractText | Our recent work showed that daily injections of osteoprotegerin (OPG)-immunoglobulin fragment complex (OPG-Fc) completely restore the function of fast-twitch extensor digitorum longus muscles in dystrophic mdx mice, a murine model of Duchenne muscular dystrophy. However, despite marked improvements, OPG-Fc was not as effective in preventing the loss of function of slow-twitch soleus and diaphragm muscles. Because beta2-agonists enhance the function of slow- and fast-twitch dystrophic muscles and because their use is limited by their adverse effects on bone and cardiac tissues, we hypothesized that OPG-Fc, a bone and skeletal muscle protector, acts synergistically with beta2-agonists and potentiates their positive effects on skeletal muscles. We observed that the content of beta2-adrenergic receptors, which are mainly expressed in skeletal muscle, is significantly reduced in dystrophic muscles but is rescued by the injection of OPG-Fc. Most important, OPG-Fc combined with a low dose of formoterol, a member of a new generation of beta2-agonists, histologically and functionally rescued slow-twitch dystrophic muscles. This combination of therapeutic agents, which have already been tested and approved for human use, may open up new therapeutic avenues for Duchenne muscular dystrophy and possibly other neuromuscular diseases. |
