Fibroblast growth factor and canonical WNT/beta-catenin signaling cooperate in suppression of chondrocyte differentiation in experimental models of FGFR signaling in cartilage

0445768 - ÚŽFG 2016 RIV NL eng J - Článek v odborném periodiku
Buchtová, Marcela - Oralová, Veronika - Aklian, A. - Mašek, J. - Veselá, I. - Ouyang, Z. - Obadalová, T. - Konečná, Ž. - Spoustová, T. - Pospíšilová, T. - Matula, P. - Vařecha, M. - Balek, L. - Gudernová, I. - Jelínková, I. - Ďuran, I. - Červenková, I. - Murakami, S. - Kozubík, Alois - Dvořák, P. - Bryja, Vítězslav - Krejčí, P.
Fibroblast growth factor and canonical WNT/beta-catenin signaling cooperate in suppression of chondrocyte differentiation in experimental models of FGFR signaling in cartilage.
Biochimica Et Biophysica Acta-Molecular Basis of Disease. Roč. 1852, č. 5 (2015), s. 839-850. ISSN 0925-4439. E-ISSN 1879-260X
Grant CEP: GA ČR GCP302/12/J059; GA ČR GBP302/12/G157; GA ČR(CZ) GA14-31540S
Institucionální podpora: RVO:67985904 ; RVO:68081707
Klíčová slova: fibroblast growth factor receptor * FGFR3 * WNT
Kód oboru RIV: EA - Morfologické obory a cytologie
Impakt faktor: 5.158, rok: 2015

Aberrant fibroblast growth factor (FGF) signaling disturbs chondrocyte differentiation in skeletal dysplasia, but the mechanisms underlying this process remain unclear. Recently, FGF was found to activate canonical WNT/beta-catenin pathway in chondrocytes via Erk MAP kinase-mediated phosphorylation of WNT co-receptor Lrp6. Here, we explore the cellular consequences of such a signaling interaction. WNT enhanced the FGF-mediated suppression of chondrocyte differentiation in mouse limb bud micromass and limb organ cultures, leading to inhibition of cartilage nodule formation in micromass cultures, and suppression of growth in cultured limbs. Simultaneous activation of the FGF and WNT/beta-catenin pathways resulted in loss of chondrocyte extracellular matrix, expression of genes typical for mineralized tissues and alteration of cellular shape. WNT enhanced the FGF-mediated downregulation of chondrocyte proteoglycan and collagen extracellular matrix via inhibition of matrix synthesis and induction of proteinases involved in matrix degradation. Expression of genes regulating RhoA GTPase pathway was induced by FGF in cooperation with WNT, and inhibition of the RhoA signaling rescued the FGF/WNT-mediated changes in chondrocyte cellular shape. Our results suggest that aberrant FGF signaling cooperates with WNT/beta-catenin in suppression of chondrocyte differentiation.
Trvalý link: http://hdl.handle.net/11104/0247821