Differential glucocorticoid effects on the fusion of Duchenne/Becker and control muscle cultures: pharmacologic detection of accelerated aging in dystrophic muscle.
We report that the glucocorticoid methylprednisolone (Mepd) enhanced myogenesis in normal primary human muscle cultures, but inhibited myogenesis of most Duchenne/Becker muscle cultures. A decline in the magnitude of myogenic stimulation of Mepd correlated with age in a random group of control patients, including some with neurologic diseases other than Duchenne/Becker dystrophy. A case of Duchenne muscular dystrophy from an exceptionally young patient yielded a muscle culture that was myogenically stimulated by Mepd. These results suggest that continuous cycles of degeneration and regeneration of dystrophic muscle in vivo may result in a change of the glucocorticoid response of the muscle progenitor cells. The glucocorticoid effects suggest caution in the long-term clinical use of these agents for muscle disease such as Duchenne muscular dystrophy.
Hardiman
O
O
Cecil B. Day Neuromuscular Research Laboratories, Massachusetts General Hospital, Charlestown.
Brown
R H
RH
Beggs
A H
AH
Specht
L
L
Sklar
R M
RM
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000473:pathology; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008775:Methylprednisolone / Q000494:pharmacology*; D008875:Middle Aged; D009132:Muscles / Q000187:drug effects* / Q000473:pathology; D009136:Muscular Dystrophies / Q000473:pathology*; D012044:Regression Analysis
D008775:Methylprednisolone