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Vol. 14, Issue 2, 545-555, February 2003

Differential Roles of Smad1 and p38 Kinase in Regulation of Peroxisome Proliferator-activating Receptor  during Bone Morphogenetic Protein 2-induced Adipogenesis

Kenji Hata,^* Riko Nishimura,^* Fumiyo Ikeda,^* Kenji Yamashita,^* Takuma Matsubara,^* Takashi Nokubi, and Toshiyuki Yoneda^*

 ^*Departments of Biochemistry and  Removable Prothodontics, Osaka University Graduate School/Faculty of Dentistry, Osaka 565-0871, Japan

Bone morphogenetic protein 2 (BMP2) promotes the differentiation of undifferentiated mesenchymal cells into adipocytes. To investigate the molecular mechanisms that regulate this differentiation process, we studied the relationship between BMP2 signaling and peroxisome proliferator-activating receptor  (PPAR) during adipogenesis of mesenchymal cells by using pluripotent mesenchymal cell line C3H10T1/2. In C3H10T1/2 cells, BMP2 induced expression of PPAR along with adipogenesis. Overexpression of Smad6, a natural antagonist for Smad1, blocked PPAR expression and adipocytic differentiation induced by BMP2. Overexpression of dominant-negative PPAR also diminished adipocytic differentiation of C3H10T1/2 cells, suggesting the central role of PPAR in BMP2-induced adipocytic differentiation. Specific inhibitors for p38 kinase inhibited BMP2-induced adipocytic differentiation and transcriptional activation of PPAR, whereas overexpression of Smad6 had no effect on transcriptional activity of PPAR. Furthermore, activation of p38 kinase by overexpression of TAK1 and TAB1, without affecting PPAR expression, led the up-regulation of transcriptional activity of PPAR. These results suggest that both Smad and p38 kinase signaling are concomitantly activated and responsible for BMP2-induced adipocytic differentiation by inducing and up-regulating PPAR, respectively. Thus, BMP2 controls adipocytic differentiation by using two distinct signaling pathways that play differential roles in this process in C3H10T1/2 cells.

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Corresponding author. E-mail address: rikonisi{at}dent.osaka-u.ac.jp.

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Molecular Biology of the Cell
Vol. 14, 545-555, February 2003
Copyright © 2003 by The American Society for Cell Biology

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