The interleukin-6/soluble interleukin-6 receptor system induces parathyroid hormone-related protein in human osteoblastic cells

被引：16

作者：

Guillén, C ^{[1
]}

de Gortázar, AR ^{[1
]}

Esbrit, P ^{[1
]}

机构：

[1] Fdn Jimenez Diaz, Res Unit, Bone & Mineral Metab Lab, E-28040 Madrid, Spain

来源：

CALCIFIED TISSUE INTERNATIONAL | 2004年 / 75卷 / 02期

关键词：

interleukin-6; interleukin-6 soluble receptor; parathyroid hormone-related protein; human osteoblasts;

D O I：

10.1007/s00223-004-0113-1

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

In the present in vitro study, we tested the hypothesis that parathyroid hormone-related protein (PTHrP) might be a mediator of interleukin-6 (IL-6) and its soluble receptor (IL-6sR) in osteoblasts. We found that IL-6, within 1-20 ng/mL, added together with IL-6sR (100 ng/mL), rapidly (I hour) increased PTHrP mRNA in human osteoblastic osteosarcoma MG-63 cells and human osteoblastic (hOB) cells from trabecular bone. PD098059, a mitogen-activated protein kinase (MAPK) kinase inhibitor, at 10 muM, and two inhibitors of protein prenylation and thus Ras activation, simvastatin (1 muM) and a farnesyltransferase (FTase) inhibitor (100 nM), but not the phosphatidylinositol 3-kinase inhibitor wortmannin, blocked the IL-6/IL-6sR-induced PTHrP expression in these cells. In addition, PD098059 as well as sirrivastatin and the FTase inhibitor abolished alkaline phosphatase activity and/or osteocalcin mRNA induction by the IL-6/IL-6sR in these cells. Our results support the role of the Ras/MAPK pathway as a major mechanism in the modulation of both PTHrP expression and differentiation in human osteoblasts.

引用

页码：153 / 159

页数：7

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