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SOCS‐2 interferes with myotube formation and potentiates osteoblast differentiation through upregulation of JunB in C2C12 cells
Author(s) -
Ouyang Xinshou,
Fujimoto Minoru,
Nakagawa Reiko,
Serada Satoshi,
Tanaka Toshio,
Nomura Shintaro,
Kawase Ichiro,
Kishimoto Tadamitsu,
Naka Tetsuji
Publication year - 2006
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.20579
Subject(s) - junb , c2c12 , osteoblast , smad , microbiology and biotechnology , downregulation and upregulation , biology , signal transduction , bone morphogenetic protein , transdifferentiation , cellular differentiation , chemistry , transcription factor , myocyte , stem cell , myogenesis , biochemistry , gene , in vitro
Suppressor of cytokine signaling (SOCS)‐2 regulates normal postnatal growth and its deficiency in mice causes gigantism with increased bone length and proportional enlargement in skeletal muscles. Using C2C12 mesenchymal precursor cell line as a model, we investigated a possible role of SOCS‐2 in the differentiation process of mesenchymal precursors. Stable transfection of SOCS‐2 into C2C12 cells resulted in the acceleration of proliferation and survival, and inhibition of spontaneous myotube formation. In addition, SOCS‐2 potentiated bone morphogenic protein (BMP)‐induced transdifferentiation of C2C12 cells into osteoblast phenotypes. These effects of SOCS‐2 on C2C12 cells differed strikingly from that of SOCS‐1, another member of SOCS family, and its mechanisms were evaluated. SOCS‐2 did not alter BMP‐induced phosphorylation and nuclear accumulation of Smad1, nor the expression of inhibitory‐Smads mRNA. However, SOCS‐2 enhanced BMP‐induced transcriptional activation of the Smad‐responsive reporter gene, suggesting that the action of SOCS‐2 is exerted at the transcriptional level. Interestingly, SOCS‐2 overexpression in C2C12 cells increased the endogenous JunB protein, one of the key transcriptional factors in the control of BMP/Smad signaling responsiveness. In addition, the proteasome inhibitor enhanced JunB protein expression in C2C12 cells. Moreover, we found that SOCS‐2 reduced JunB ubiquitination in COS‐7 cells. Although SOCS‐2 is a modulator of growth hormone (GH) signaling, the upregulation of JunB by SOCS‐2 did not require GH signaling. Taken together, these results suggest that SOCS‐2 positively regulates endogenous JunB protein expression in C2C12 cells through inhibition of JunB destabilization by the ubiquitin–proteasome pathway, and thereby regulates the cell fate of mesenchymal precursors. J. Cell. Physiol. 207: 428–436, 2006. © 2006 Wiley‐Liss, Inc.