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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
Abstract:
Human bone cell line (SaOS2) express different mRNAs involved in bone biology and physiology such as estrogen receptor α (ERα), estrogen receptor β (ERβ), vitamin D receptor (VDR), 1α, 25 hydroxy vitamin D(3) hydroxylase (1OHase) as well as 12 and 15 lipoxygenases (12LO and 15LO). These mRNAs are modulated by estrogenic compounds. Since the skeletal protective effects of estrogens are not discernible in diabetic women, we tested whether the expression of the parameters measured here and their modulations by estrogens, in SaOS2 cells grown in growth medium containing high glucose (HG; 9.0 g/L; 44 mM) compared to normal glucose (NG; 4.5 g/L; 22 mM). High Glucose (HG) significantly increased DNA synthesis and creatine kinase (CK) specific activity in SaOS2 cells. Stimulations of DNA but not of CK by E(2), by 4, 4', 4''-[4-propyl-(1H)-pyrazol-1, 3, 5- triyl] tris-phenol (PPT, ERα specific agonist), or by 2, 3-bis (4-hydroxyphenyl)-propionitrile (DPN, ERβ specific agonist), were abolished by HG. HG itself upregulated the expression of mRNA of 12LO and 15LO and upregulated to much less extent of ERβ and VDR, but had no effect on the expression of mRNA of ERα and 1OHase. The different hormonal treatments modulated the expressions of 12LO and 15LO mRNAs which was reduced in HG, whereas the induction of their products 12HETE and 15HETE was only slightly affected by HG. The exact mechanism of HG effects on bone cell responses is yet to be investigated and its relationship to human bone physiology is not yet clear.
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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