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

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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 17β-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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Authors and Affiliations

  1. Department of Clinical Laboratory, The Second Xiang-Ya Hospital of Central South University, ChangSha, China

    Y. H. Bu, X. B. Luo, L. L. Tang & A. G. Tang MD

  2. Department of Orthopaedics, The Second Xiang-Ya Hospital of Central South University, ChangSha, China

    D. Peng

  3. Institute of Endocrinology and Metabolism, The Second Xiang-Ya Hospital of Central South University, ChangSha, China

    H. D. Zhou, Q. X. Huang & W. Liu

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  1. Y. H. Bu
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  4. Q. X. Huang
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  5. W. Liu
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  6. X. B. Luo
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  7. L. L. Tang
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Correspondence to A. G. Tang MD.

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These two authors contributed equally to this work.

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Bu, Y.H., Peng, D., Zhou, H.D. et al. Insulin receptor substrate 2 plays important roles in 17β-estradiol-induced bone formation. J Endocrinol Invest 32, 682–689 (2009). https://doi.org/10.1007/BF03345741

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  • DOI: https://doi.org/10.1007/BF03345741

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