Retinoic acid inhibits BMP4-induced C3H10T1/2 stem cell commitment to adipocyte via downregulating Smad/p38MAPK signaling

Jeong Soon Lee, Jin Hee Park, Il Keun Kwon, Jung Yul Lim

Research output: Contribution to journalArticle

24 Scopus citations

Abstract

Increased adipocyte formation from mesenchymal stem cells (MSCs) is typical for obesity. It is recently observed that bone morphogenetic proteins (BMPs) provide instructive signals for the commitment of MSCs to adipocytes. We examined potential role of retinoic acid (RA) in inhibiting the BMP4 induction of MSC commitment toward adipocyte. BMP4-treated C3H10T1/2 MSCs, when further exposed to adipogenic differentiation media, displayed distinct adipocytic commitment and differentiation. This could be inhibited by RA exposure during the BMP4 treatment stage (commitment stage before adipogenic hormonal inducers were given), as was observed by reductions in key adipogenic genes/transcription factors (C/EBPα, PPARγ, aP2), lipogenic genes (LPL, FAS, GLUT4), and lipid accumulation. Among RA receptors (RARs) screened, RARβ was mainly upregulated under RA exposure. BMP4 signaled through both Smad1/5/8 and p38 mitogen-activated protein kinase (MAPK) and RA significantly suppressed the BMP4-triggered phosphorylation of both Smad1/5/8 and p38MAPK. These data suggest that RA has inhibitory effects on the BMP4 induction of C3H10T1/2 adipocytic commitment via downregulating Smad/p38MAPK signaling. How to inhibit MSC adipocytic commitment, as partly revealed in this study, will have a significant impact on treating obesity and related diseases.

Original languageEnglish (US)
Pages (from-to)550-555
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume409
Issue number3
DOIs
StatePublished - Jun 10 2011

Keywords

  • Adipogenesis
  • Bone morphogenetic proteins
  • Mesenchymal stem cells
  • Obesity
  • P38MAPK
  • Retinoic acid
  • Smad

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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