Phorbol 12-myristate 13-acetate (PMA) suppresses high Ca2+-enhanced adipogenesis in bone marrow stromal cells

J Physiol Sci. 2019 Sep;69(5):741-748. doi: 10.1007/s12576-019-00690-9. Epub 2019 Jun 29.

Abstract

We have previously reported that increased extracellular and intracellular Ca2+ lead to adipocyte accumulation in bone marrow stromal cells (BMSCs). However, strategies to suppress high Ca2+-enhanced adipocyte accumulation have not been reported. We examined the effects of the diacylglycerol analog phorbol 12-myristate 13-acetate (PMA) on proliferation and adipogenesis of mouse primary BMSCs. We used 9 mM CaCl2 and 100 nM ionomycin to increase extracellular Ca2+ and intracellular Ca2+, respectively. PMA suppressed the expression of both C/EBPα and PPARγ under normal adipogenesis, adipogenesis + CaCl2, and adipogenesis + ionomycin conditions. PMA enhanced proliferation under normal adipogenesis conditions but suppressed proliferation under adipogenesis + CaCl2 and adipogenesis + ionomycin conditions. PMA did not affect the accumulation of adipocytes under normal adipogenesis conditions but suppressed adipocyte accumulation under adipogenesis + CaCl2 and adipogenesis + ionomycin conditions. These results suggest that the PMA-dependent pathway is an important signaling pathway to suppress high Ca2+-enhanced adipocyte accumulation.

Keywords: Adipocytes; Bone marrow stromal cells; Diacylglycerol; Extracellular Ca2+; Intracellular Ca2+; PMA.

MeSH terms

  • Adipocytes / drug effects
  • Adipocytes / metabolism
  • Adipogenesis / drug effects*
  • Animals
  • Calcium / metabolism*
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Ionomycin / pharmacology
  • Male
  • Mesenchymal Stem Cells / drug effects*
  • Mesenchymal Stem Cells / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Tetradecanoylphorbol Acetate / pharmacology*

Substances

  • Ionomycin
  • Tetradecanoylphorbol Acetate
  • Calcium