QUICK SEARCH:   [advanced] Author: Keyword(s):
Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents

First published online 18 October 2005
doi: 10.1242/jcs.02618

This Article Figures Only Full Text Full Text (PDF) All Versions of this Article: jcs.02618v1 118/21/5089    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Krejci, P. Articles by Wilcox, W. R. Search for Related Content PubMed PubMed Citation Articles by Krejci, P. Articles by Wilcox, W. R.

Interaction of fibroblast growth factor and C-natriuretic peptide signaling in regulation of chondrocyte proliferation and extracellular matrix homeostasis

¹ Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
² INSERM U589, Institut Louis Bugnard, 31403 Toulouse, France
³ Orthopaedic Research Laboratories, University of Washington, Seattle, WA 98195, USA
⁴ Department of Pediatrics, UCLA School of Medicine, CA 90095, USA

^* Author for correspondence (e-mail: william.wilcox{at}cshs.org)

Accepted 8 August 2005

Overexpression of C-natriuretic peptide (CNP) in cartilage partially rescues achondroplasia in the mouse. Here, we studied the interaction of fibroblast growth factor (FGF) and CNP signaling in chondrocytes. CNP antagonized FGF2-induced growth arrest of rat chondrosarcoma (RCS) chondrocytes by inhibition of the Erk mitogen activated protein kinase pathway. This effect of CNP was protein kinase G-dependent and was mimicked by the cGMP analog pCPT-cGMP. FGF2-mediated activation of both MEK and Raf-1 but not Ras or FRS2 was abolished by CNP demonstrating that CNP blocks the Erk pathway at the level of Raf-1. CNP also counteracted the FGF2-mediated degradation of RCS extracellular matrix. CNP partially antagonized FGF2-induced expression, release and activation of several matrix-remodeling molecules including matrix metalloproteinase 2 (MMP2), MMP3, MMP9, MMP10 and MMP13. In addition, CNP compensated for FGF2-mediated matrix loss by upregulation of matrix production independent of its interference with FGF signaling. We conclude that CNP utilizes both direct and indirect ways to counteract the effects of FGF signaling in a chondrocyte environment.

Key words: Fibroblast growth factor, C-natriuretic peptide, Mitogen-activated protein kinase, Growth arrest, Extracellular Matrix, Chondrocyte

This article has been cited by other articles:

				P. Krejci, L. Salazar, H. S. Goodridge, T. A. Kashiwada, M. J. Schibler, P. Jelinkova, L. M. Thompson, and W. R. Wilcox STAT1 and STAT3 do not participate in FGF-mediated growth arrest in chondrocytes J. Cell Sci., February 1, 2008; 121(3): 272 - 281. [Abstract] [Full Text] [PDF]

				P. Moffatt, G. Thomas, K. Sellin, M.-C. Bessette, F. Lafreniere, O. Akhouayri, R. St-Arnaud, and C. Lanctot Osteocrin Is a Specific Ligand of the Natriuretic Peptide Clearance Receptor That Modulates Bone Growth J. Biol. Chem., December 14, 2007; 282(50): 36454 - 36462. [Abstract] [Full Text] [PDF]

				P. Krejci, B. Masri, L. Salazar, C. Farrington-Rock, H. Prats, L. M. Thompson, and W. R. Wilcox Bisindolylmaleimide I Suppresses Fibroblast Growth Factor-mediated Activation of Erk MAP Kinase in Chondrocytes by Preventing Shp2 Association with the Frs2 and Gab1 Adaptor Proteins J. Biol. Chem., February 2, 2007; 282(5): 2929 - 2936. [Abstract] [Full Text] [PDF]

				G. Karakiulakis, E. Papakonstantinou, A. J. Aletras, M. Tamm, and M. Roth Cell Type-specific Effect of Hypoxia and Platelet-derived Growth Factor-BB on Extracellular Matrix Turnover and Its Consequences for Lung Remodeling J. Biol. Chem., January 12, 2007; 282(2): 908 - 915. [Abstract] [Full Text] [PDF]