title: Osteoprotegerin and β2-Agonists Mitigate Muscular Dystrophy in Slow- and Fast-Twitch Skeletal Muscles.
abstract: 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 β2-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 β2-agonists and potentiates their positive effects on skeletal muscles. We observed that the content of β2-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 β2-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.
authors.affiliation: Centre Hospitalier Universitaire de Québec-Centre de Recherche du Centre Hospitalier de l'Université Laval, Université Laval, Quebec City, Quebec, Canada.
authors.forename: Sébastien S
authors.initials: SS
authors.lastname: Dufresne
authors.affiliation: Centre Hospitalier Universitaire de Québec-Centre de Recherche du Centre Hospitalier de l'Université Laval, Université Laval, Quebec City, Quebec, Canada.
authors.forename: Antoine
authors.initials: A
authors.lastname: Boulanger-Piette
authors.affiliation: Centre Hospitalier Universitaire de Québec-Centre de Recherche du Centre Hospitalier de l'Université Laval, Université Laval, Quebec City, Quebec, Canada; Department of Rehabilitation, Faculty of Medicine, Université Laval, Quebec City, Quebec, Canada. Electronic address: jerome.frenette@crchul.ulaval.ca.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Frenette
mesh_terms: D058666:Adrenergic beta-2 Receptor Agonists / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D000068759:Formoterol Fumarate / Q000494:pharmacology / Q000627:therapeutic use; D007249:Inflammation / Q000473:pathology; D008297:Male; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D018656:Muscle Fibers, Fast-Twitch / Q000187:drug effects / Q000473:pathology*; D018657:Muscle Fibers, Slow-Twitch / Q000187:drug effects / Q000473:pathology*; D009137:Muscular Dystrophy, Animal / Q000188:drug therapy / Q000473:pathology; D053244:Osteoprotegerin / Q000494:pharmacology / Q000627:therapeutic use*; D011961:Receptors, Fc / Q000378:metabolism
chemical_list: D058666:Adrenergic beta-2 Receptor Agonists; D053244:Osteoprotegerin; D011961:Receptors, Fc; D000068759:Formoterol Fumarate