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

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 D3 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 E2, 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.