title: Inhibition of glycogen synthase kinase-3β attenuates glucocorticoid-induced suppression of myogenic differentiation in vitro.
abstract: Glucocorticoids are the only therapy that has been demonstrated to alter the progress of Duchenne muscular dystrophy (DMD), the most common muscular dystrophy in children. However, glucocorticoids disturb skeletal muscle metabolism and hamper myogenesis and muscle regeneration. The mechanisms involved in the glucocorticoid-mediated suppression of myogenic differentiation are not fully understood. Glycogen synthase kinase-3β (GSK-3β) is considered to play a central role as a negative regulator in myogenic differentiation. Here, we showed that glucocorticoid treatment during the first 48 h in differentiation medium decreased the level of phosphorylated Ser9-GSK-3β, an inactive form of GSK-3β, suggesting that glucocorticoids affect GSK-3β activity. We then investigated whether GSK-3β inhibition could regulate glucocorticoid-mediated suppression of myogenic differentiation in vitro. Two methods were employed to inhibit GSK-3β: pharmacological inhibition with LiCl and GSK-3β gene knockdown. We found that both methods resulted in enhanced myotube formation and increased levels of muscle regulatory factors and muscle-specific protein expression. Importantly, GSK-3β inhibition attenuated glucocorticoid-induced suppression of myogenic differentiation. Collectively, these data suggest the involvement of GSK-3β in the glucocorticoid-mediated impairment of myogenic differentiation. Therefore, the inhibition of GSK-3β may be a strategy for preventing glucocorticoid-induced muscle degeneration.
authors.affiliation: Department of Neurology, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, China.
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Ma
authors.affiliation: Department of Neurology, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, China.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Zhong
authors.affiliation: Department of Neurology, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, China.
authors.forename: Zhenyang
authors.initials: Z
authors.lastname: Zheng
authors.affiliation: Institute of Molecular Medicine and Genetics, Georgia Regents University, Augusta, Georgia, United States of America.
authors.forename: Xing-Ming
authors.initials: XM
authors.lastname: Shi
authors.affiliation: Department of Neurology, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, China.
authors.forename: Weixi
authors.initials: W
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D003907:Dexamethasone / Q000494:pharmacology; D005938:Glucocorticoids / Q000494:pharmacology; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D018021:Lithium Chloride / Q000494:pharmacology*; D008810:Mice, Inbred C57BL; D024510:Muscle Development; D032446:Myoblasts / Q000502:physiology*; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational
chemical_list: D005938:Glucocorticoids; D003907:Dexamethasone; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; D038362:Glycogen Synthase Kinase 3; D018021:Lithium Chloride