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Isolation and Differentiation of Adipose-Derived Stem Cells from Porcine Subcutaneous Adipose Tissues
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Isolation and Differentiation of Adipose-Derived Stem Cells from Porcine Subcutaneous Adipose Tissues

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20(S)-hydroxycholesterol inhibits PPARgamma expression and adipogenic differentiation of bone marrow stromal cells

Woo-Kyun Kim1, Vicente Meliton, Christopher M Amantea

  • 1Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.

Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research
|July 20, 2007
PubMed
Abstract

Insights

The osteogenic oxysterol 20(S)-hydroxycholesterol inhibits adipocyte differentiation by suppressing PPARgamma expression through a hedgehog-dependent pathway. This finding offers insights into bone marrow stromal cell differentiation and potential therapeutic targets for osteoporosis.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Background:

  • Multipotent bone marrow stromal cells (MSCs) differentiate into osteoblasts and adipocytes.
  • Reciprocal differentiation of MSCs influences bone and fat formation, particularly in aging and osteoporosis.
  • Specific oxysterols, including 20(S)-hydroxycholesterol, have demonstrated pro-osteogenic and anti-adipogenic properties.

Purpose of the Study:

  • To investigate the molecular mechanisms by which oxysterols inhibit adipogenic differentiation.
  • To determine if the hedgehog signaling pathway mediates the anti-adipogenic effects of 20(S)-hydroxycholesterol.
  • To assess the impact of 20(S)-hydroxycholesterol on peroxisome proliferator-activated receptor gamma (PPARgamma) expression during adipogenesis.

Main Methods:

  • Utilized the M2-10B4 murine MSC line.
  • Assessed the effects of 20(S)-hydroxycholesterol and sonic hedgehog (Shh) on adipogenic differentiation and PPARgamma expression.
  • Employed RT-qPCR, promoter activity assays, and statistical analysis (ANOVA).

Main Results:

  • 20(S)-hydroxycholesterol completely inhibited troglitazone-induced adipocyte formation and PPARgamma mRNA induction in MSCs.
  • The inhibitory effects of 20(S)-hydroxycholesterol on adipogenesis and PPARgamma expression were reversed by the hedgehog signaling inhibitor cyclopamine.
  • 20(S)-hydroxycholesterol and Shh suppressed PPARgamma2 promoter activity, indicating regulation at the transcriptional level.

Conclusions:

  • The anti-adipogenic effects of 20(S)-hydroxycholesterol in murine MSCs are mediated by a hedgehog-dependent mechanism.
  • Inhibition of PPARgamma expression is a key factor in the anti-adipogenic action of this oxysterol.
  • These findings elucidate the molecular pathways involved in oxysterol-mediated regulation of MSC differentiation, relevant to bone health and metabolic disorders.

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