Volume 21, No 2, Feb 2011
ISSN: 1001-0602
EISSN: 1748-7838 2018
impact factor 17.848*
(Clarivate Analytics, 2019)
Volume 21 Issue 2, February 2011: 350-364
ORIGINAL ARTICLES
Oncostatin M inhibits myoblast differentiation and regulates muscle regeneration
Fang Xiao1,*, Haixia Wang1,*, Xinrong Fu1, Yanfeng Li1, Kewei Ma1,3, Luguo Sun1,4 Xiang Gao2 and Zhenguo Wu1
1Department of Biochemistry, Hong Kong University of Science & Technology, Clear Water Bay, Kowloon, Hong Kong, China
2Model Animal Research Center, Nanjing University, Nanjing 201161, China
3Current address: Department of Hematology and Oncology, The First Hospital, Jilin University, Changchun, China.
4Current address: Department of Molecular Biology, Collage of Basic Medicine, Jilin University, Changchun, China
Correspondence: Zhenguo Wu,(bczgwu@ust.hk)
Oncostatin M (OSM) is a cytokine of the interleukin-6 family and plays important roles during inflammation. However, its roles in myoblast differentiation and muscle regeneration remain unexplored. We show here that OSM potently inhibited myoblast differentiation mainly by activating the JAK1/STAT1/STAT3 pathway. OSM downregulated myocyte enhancer-binding factor 2A (MEF2A), upregulated the expression of Id1 and Id2, and inhibited the transcriptional activity of MyoD and MEF2. In addition, OSM also enhanced the expression of STAT3 and OSM receptor, which constituted a positive feedback loop to further amplify OSM-induced signaling. Moreover, we found that STAT1 physically associated with MEF2 and repressed its transcriptional activity, which could account for the OSM-mediated repression of MEF2. Although undetectable in normal muscles in vivo, OSM was rapidly induced on muscle injury and then promptly downregulated just before the majority of myoblasts differentiate. Prolonged expression of OSM in muscles compromised the regeneration process without affecting myoblast proliferation, suggesting that OSM functions to prevent proliferating myoblasts from premature differentiation during the early phase of muscle regeneration.
Cell Research (2011) 21: 350-364. doi:10.1038/cr.2010.144; published online 19 October 2010
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