Estrogens and hyperglycemic modulation of mRNAs expressions involved in bone metabolism: an overshadowed association?

Dalia Somjen1, Sara Katzburg, Orli Sharon

  • 1Institute of Endocrinology, Metabolism and Hypertension, Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel. dalias@tlvmc.gov.il

Insights

High glucose impairs estrogen

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Endocrinology

Background:

  • Human bone cells (SaOS2) express key mRNAs for bone health, including estrogen receptors (ERα, ERβ), vitamin D receptor (VDR), and lipoxygenases (12LO, 15LO).
  • Estrogenic compounds modulate these mRNA expressions, influencing bone physiology.

Purpose of the Study:

  • To investigate the impact of high glucose (HG) on SaOS2 cell gene expression and estrogen responsiveness.
  • To determine if HG affects the modulation of bone-related mRNAs by estrogenic compounds.

Main Methods:

  • SaOS2 cells were cultured in normal glucose (NG) and high glucose (HG) media.
  • Cells were treated with estradiol (E2), ERα agonist (PPT), and ERβ agonist (DPN).
  • mRNA expression of ERα, ERβ, VDR, 1OHase, 12LO, and 15LO was analyzed using quantitative PCR.

Main Results:

  • HG significantly increased DNA synthesis and creatine kinase (CK) activity in SaOS2 cells.
  • HG abolished the stimulatory effects of E2, PPT, and DPN on DNA synthesis.
  • HG upregulated 12LO and 15LO mRNA expression, with minor increases in ERβ and VDR mRNA; ERα and 1OHase mRNA remained unaffected.

Conclusions:

  • High glucose conditions in SaOS2 cells disrupt estrogen signaling pathways crucial for bone health.
  • HG alters the expression of lipoxygenase enzymes, potentially impacting bone cell function.
  • Further research is needed to elucidate the precise mechanisms of HG effects on bone cell responses and their clinical relevance in conditions like diabetes.

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