BACKGROUND: Discovering the mechanisms of the estrogen effects on the osteoblasts is very important for the development of new agents which have the clear-cut beneficial effects of estrogen while free of adverse effect. AIM: The aim of this study was to investigate the differential gene expression of 17beta-estradiol (E2)-treated osteoblast-like cells, and the effect of E2 on the insulin receptor substrate 2 (IRS- 2) expression in human cultured osteoblast-like cells and the osteoblasts of ovariectomized (OVX) rats. MATERIAL AND METHODS: The differential gene expression of E2-treated osteoblast- like cells was analyzed by cytokine expression array and validated by RT-PCR and Western blot analysis. The protein expression and phosphorylation of one of the differentially expressed gene, IRS-2, treated at different times with E2 were analyzed. The Sprague-Dawley rats were ovariectomized and then treated with E2, the IRS-2 expression was analyzed by immunohistochemistry analysis. RESULTS: E2 upregulated the mRNA expression of IRS-2, bone morphogenetic protein 9, and connective tissue growth factor expression, down-regulated the mRNA expression of matrix metalloproteinase 15 and some tumor suppressor genes. Peak expression of IRS-2 was observed at 12-24 h of treatment by 10-8M E2. E2 can also increase the phosphorylation of IRS-2. The IRS-2 expression was down-regulated in the osteoblasts and bone marrow cells of the OVX rats, which had lower bone mineral density (BMD) than the normal rats. However, both BMD and IRS-2 expression can be rescued by 10-8M E2 in the OVX rats. CONCLUSION: IRS-2 in osteoblast is up-regulated by E2 and plays important roles in the estrogen- induced bone formation.
BACKGROUND: Discovering the mechanisms of the estrogen effects on the osteoblasts is very important for the development of new agents which have the clear-cut beneficial effects of estrogen while free of adverse effect. AIM: The aim of this study was to investigate the differential gene expression of 17beta-estradiol (E2)-treated osteoblast-like cells, and the effect of E2 on the insulin receptor substrate 2 (IRS- 2) expression in human cultured osteoblast-like cells and the osteoblasts of ovariectomized (OVX) rats. MATERIAL AND METHODS: The differential gene expression of E2-treated osteoblast- like cells was analyzed by cytokine expression array and validated by RT-PCR and Western blot analysis. The protein expression and phosphorylation of one of the differentially expressed gene, IRS-2, treated at different times with E2 were analyzed. The Sprague-Dawley rats were ovariectomized and then treated with E2, the IRS-2 expression was analyzed by immunohistochemistry analysis. RESULTS:E2 upregulated the mRNA expression of IRS-2, bone morphogenetic protein 9, and connective tissue growth factor expression, down-regulated the mRNA expression of matrix metalloproteinase 15 and some tumor suppressor genes. Peak expression of IRS-2 was observed at 12-24 h of treatment by 10-8M E2. E2 can also increase the phosphorylation of IRS-2. The IRS-2 expression was down-regulated in the osteoblasts and bone marrow cells of the OVX rats, which had lower bone mineral density (BMD) than the normal rats. However, both BMD and IRS-2 expression can be rescued by 10-8M E2 in the OVX rats. CONCLUSION:IRS-2 in osteoblast is up-regulated by E2 and plays important roles in the estrogen- induced bone formation.
Authors: Claudie Berger; Lisa Langsetmo; Lawrence Joseph; David A Hanley; K Shawn Davison; Robert G Josse; Jerilynn C Prior; Nancy Kreiger; Alan Tenenhouse; David Goltzman Journal: J Bone Miner Res Date: 2009-02 Impact factor: 6.741
Authors: G Koricanac; T Milosavljevic; M Stojiljkovic; Z Zakula; N Ribarac-Stepic; E R Isenovic Journal: J Steroid Biochem Mol Biol Date: 2007-09-07 Impact factor: 4.292