RGD Reference Report - Insulin Receptor Substrate 2 plays Important Roles in 17betaEstradiol Induced Bone Formation.

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Insulin Receptor Substrate 2 plays Important Roles in 17betaEstradiol Induced Bone Formation.
Authors:	Bu, YH Peng, D Zhou, HD Huang, QX Liu, W Luo, XB Tang, LL Tang, AG
Citation:	Bu YH, etal., J Endocrinol Invest. 2009 May 26.
RGD ID:	2314504
Pubmed:	PMID:19509476 (View Abstract at PubMed)
DOI:	DOI:10.3275/6328 (Journal Full-text)
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: In order to investigate the differential expressed gene of 17betaEstradiol (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 differential expressed gene, IRS-2, at different treated time by E2 were analyzed. The Sprague -Dawley rats were ovariectomized and then treated by E2, the IRS-2 expression was analyzed by immunohistochemistry analysis. Results: E2 up-regulated the mRNA expression of IRS-2, bone morphogenetic protein 9 and connective tissue growth factor expression, down-regulates the mRNA expression of matrix metalloproteinase 15 and some tumor suppressor genes. Peak expression of IRS-2 was observed at 12-24 hours 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 has the low 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 17betaEstradiol and plays important roles in the estrogen induced bone formation.

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Object Symbol	Species	Term	Qualifier	Evidence	With	Notes	Source	Original Reference(s)
Ccn2	Rat	response to estradiol		IEP		17 beta-estradiol	RGD
Mmp15	Rat	response to estradiol		IEP			RGD

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Genes (Rattus norvegicus)

Ccn2 (cellular communication network factor 2)

Mmp15 (matrix metallopeptidase 15)

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Insulin Receptor Substrate 2 plays Important Roles in 17betaEstradiol Induced Bone Formation.