Insulin receptor substrate 1 regulates the cellular differentiation and the matrix metallopeptidase expression of preosteoblastic cells

被引：24

作者：

Bu, Yan-Hong ^{[1
,2
]}

He, Yu-Ling ^{[1
]}

Zhou, Hou-De ^{[1
]}

Liu, Wei ^{[1
]}

Peng, Dan ^{[3
]}

Tang, Ai-Guo ^{[2
]}

Tang, Ling-Li ^{[2
]}

Xie, Hui ^{[1
]}

Huang, Qiu-Xia ^{[1
]}

Luo, Xiang-Hang ^{[1
]}

Liao, Er-Yuan ^{[1
]}

机构：

[1] Cent S Univ, Xiang Ya Hosp 2, Inst Metab & Endocrinol, Changsha 410011, Hunan, Peoples R China

[2] Cent S Univ, Xiang Ya Hosp 2, Dept Clin Lab, Changsha 410011, Hunan, Peoples R China

[3] Cent S Univ, Xiang Ya Hosp 2, Dept Orthopaed, Changsha 410011, Hunan, Peoples R China

来源：

JOURNAL OF ENDOCRINOLOGY | 2010年 / 206卷 / 03期

基金：

中国国家自然科学基金;

关键词：

BONE LOSS; IN-VITRO; OSTEOBLAST; MT1-MMP; METALLOPROTEINASES; RESORPTION; ACTIVATOR; PROTEINS; HORMONE; LIGAND;

D O I：

10.1677/JOE-10-0064

中图分类号：

R5 [内科学];

学科分类号：

100201 [内科学];

摘要：

Insulin receptor substrate 1 (IRS1) is an essential molecule for the intracellular signaling of IGF1 and insulin, which are potent anabolic regulators of bone metabolism. Osteoblastic IRS1 is essential for maintaining bone turnover; however, the mechanism underlying this regulation remains unclear. To clarify the role of IRS1 in bone metabolism, we employed RNA interference to inhibit IRS1 gene expression and observed the effects of silencing this gene on the proliferation and differentiation of and the expression of matrix metallopeptidase (MMP) and tumor necrosis factor receptor superfamily, member 11b (TNFRSF11B) in MC3T3-E1 cells. Our results showed that IRS1 short hairpin RNAs can effectively suppress the expression of IRS1, and inhibit the phosphorylation of AKT in IRS1 pathway; reduce the expression of MMP2, MMP3, MMP13, and MMP14, decrease the expression of TNFRSF11B and RANKL (also known as tumor necrosis factor (ligand) superfamily, member 11), however increase the RANKL/TNFRSF11B ratio; decrease cell survival, proliferation, and mineralization, and impair the differentiation of MC3T3-E1 cells. The downregulation of IRS1 had no effect on the expression of MMP1. Our findings suggest that IRS1 not only promotes bone formation and mineralization but also might play roles in bone resorption partly via the regulation of MMPs and RANKL/TNFRSF11B ratio, thus regulates the bone turnover. Journal of Endocrinology (2010) 206, 271-277

引用

页码：271 / 277

页数：7

共 31 条

[1]

Insulin receptor substrate-2 maintains predominance of anabolic function over catabolic function of osteoblasts [J].