Differential roles of Smad1 and p38 kinase in regulation of peroxisome proliferator-activating receptor γ during bone morphogenetic protein 2-induced adipogenesis

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

    Research output: Contribution to journalArticlepeer-review

    142 Citations (Scopus)

    Abstract

    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 γ (PPARγ) during adipogenesis of mesenchymal cells by using pluripotent mesenchymal cell line C3H10T1/2. In C3H10T1/2 cells, BMP2 induced expression of PPARγ along with adipogenesis. Overexpression of Smad6, a natural antagonist for Smad1, blocked PPARγ expression and adipocytic differentiation induced by BMP2. Overexpression of dominant-negative PPARγ also diminished adipocytic differentiation of C3H10T1/2 cells, suggesting the central role of PPARγ in BMP2-induced adipocytic differentiation. Specific inhibitors for p38 kinase inhibited BMP2-induced adipocytic differentiation and transcriptional activation of PPARγ, whereas overexpression of Smad6 had no effect on transcriptional activity of PPARγ. Furthermore, activation of p38 kinase by overexpression of TAK1 and TAB1, without affecting PPARγ expression, led the up-regulation of transcriptional activity of PPARγ. 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 PPARγ, respectively. Thus, BMP2 controls adipocytic differentiation by using two distinct signaling pathways that play differential roles in this process in C3H10T1/2 cells.

    Original languageEnglish
    Pages (from-to)545-555
    Number of pages11
    JournalMolecular biology of the cell
    Volume14
    Issue number2
    DOIs
    Publication statusPublished - 2003 Feb 1

    ASJC Scopus subject areas

    • Molecular Biology
    • Cell Biology

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