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. 2009 Sep;32(8):682-9.
doi: 10.1007/BF03345741. Epub 2009 May 26.

Insulin receptor substrate 2 plays important roles in 17beta-estradiol-induced bone formation

Y-H Bu  1 , D Peng, H-D Zhou, Q-X Huang, W Liu, X-B Luo, L-L Tang, A-G Tang
Affiliations

Insulin receptor substrate 2 plays important roles in 17beta-estradiol-induced bone formation

Y-H Bu et al. J Endocrinol Invest. 2009 Sep.

Abstract

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.

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