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Calcified Tissue International
Published in: Calcified Tissue International 2/2004

01-08-2004

The Interleukin-6/Soluble Interleukin-6 Receptor System Induces Parathyroid Hormone–Related Protein in Human Osteoblastic Cells

Authors: C. Guillén, A. R. de Gortázar, P. Esbrit

Published in: Calcified Tissue International | Issue 2/2004

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Abstract

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 (1 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 μM, and two inhibitors of protein prenylation and thus Ras activation, simvastatin (1 μM) 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 simvastatin 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.
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Metadata
Title
The Interleukin-6/Soluble Interleukin-6 Receptor System Induces Parathyroid Hormone–Related Protein in Human Osteoblastic Cells
Authors
C. Guillén
A. R. de Gortázar
P. Esbrit
Publication date
01-08-2004
Publisher
Springer-Verlag
Published in
Calcified Tissue International / Issue 2/2004
Print ISSN: 0171-967X
Electronic ISSN: 1432-0827
DOI
https://doi.org/10.1007/s00223-004-0113-1

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