Deflazacort but not prednisone improves both muscle repair and fiber growth in diaphragm and limb muscle in vivo in the mdx dystrophic mouse.
The effects of the glucocorticoids deflazacort and prednisone on mdx mouse dystrophy and muscle regeneration were evaluated in a 4.5-week double-blind study to test whether they would decrease dystrophy by anti-inflammatory effects [in intact diaphragm and left tibialis anterior (TA) muscle] and increase new muscle formation (after crush injury). In the left TA, fiber diameter was greater after deflazacort and prednisone compared to placebo. However, only deflazacort increased the centronucleation index of accumulated damage and repair, and myotube growth over the long term. In crush-injured TA, the fusion of proliferative muscle precursors to myotubes (by autoradiography) was increased only after deflazacort. Diaphragm muscle was much less inflamed, and fiber diameter was greater after deflazacort. Results suggest that glucocorticoids decreased the severe phenotype of dystrophy in the mdx diaphragm. Moreover, deflazacort uniquely promoted myogenic repair over short and longer terms, in addition to stimulating fiber growth. These first clues to the targets of deflazacort action on muscle repair have important positive implications for treating Duchenne dystrophy.
Anderson
J E
JE
Department of Anatomy, University of Manitoba, Winnipeg, Canada.
McIntosh
L M
LM
Poettcker
R
R
D000818:Animals; D003964:Diaphragm / Q000473:pathology / Q000503:physiopathology*; D007866:Leg; D051379:Mice; D018101:Mice, Inbred mdx; D018485:Muscle Fibers, Skeletal / Q000502:physiology; D009132:Muscles / Q000187:drug effects* / Q000293:injuries / Q000503:physiopathology; D009137:Muscular Dystrophy, Animal / Q000503:physiopathology*; D009220:Myositis / Q000503:physiopathology; D011241:Prednisone / Q000494:pharmacology*; D011282:Pregnenediones / Q000494:pharmacology*; D012038:Regeneration; D014949:Wounds, Nonpenetrating / Q000473:pathology / Q000503:physiopathology
D011282:Pregnenediones; C021988:deflazacort; D011241:Prednisone