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Published on: August 13, 2019
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 64239, and the Sackler Faculty of Medicine, Tel- Aviv University , Tel- Aviv , ISRAEL.
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; 9.0g/L; 44mM) compared to normal glucose (NG; 4.5g/L; 22mM). HG significantly increased DNA synthesis (DNA) and creatine kinase specific activity (CK) 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 up regulated the expression of mRNA of 12LO and 15LO and up regulated to much less extent 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 12 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 levels impair estrogen
Area of Science:
- Endocrinology
- Bone Biology
- Cellular Physiology
Background:
- Estrogen receptors (ERα, ERβ), vitamin D receptor (VDR), and lipoxygenases (12LO, 15LO) are key in bone health.
- Estrogen's protective effects on bone are less clear in diabetic women.
- High glucose (HG) may interfere with these pathways in bone cells.
Purpose of the Study:
- To investigate the impact of HG on gene expression and estrogen modulation in human bone cells (SaOS2).
- To determine if HG affects ERα, ERβ, VDR, 1OHase, 12LO, and 15LO mRNA expression and their response to 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 target genes and DNA synthesis were analyzed.
Main Results:
- HG increased DNA synthesis and creatine kinase activity.
- HG abolished estrogenic compound-induced DNA synthesis stimulation.
- HG upregulated 12LO and 15LO mRNA, and to a lesser extent ERβ and VDR mRNA, while not affecting ERα or 1OHase mRNA.
Conclusions:
- High glucose disrupts estrogen signaling pathways in bone cells.
- HG alters the expression of key genes involved in bone metabolism and inflammation.
- Further research is needed to clarify the mechanisms and implications for bone health in diabetes.
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