BUCHTOVÁ, marcela, Veronika ORALOVÁ, Anie AKLIAN, Jan MAŠEK, Iva VESELA, Zhufeng OUYANG, Tereza OBADALOVÁ, Žaneta KONEČNÁ, Tereza SPOUSTOVÁ, Tereza POSPÍŠILOVÁ, Petr MATULA, Miroslav VAŘECHA, Lukáš BÁLEK, Iva GUDERNOVÁ, Iva JELÍNKOVÁ, Ivan DURAN, Iveta ČERVENKOVÁ, Shunichi MURAKAMI, Alois KOZUBÍK, Petr DVOŘÁK, Vítězslav BRYJA and Pavel KREJČÍ. 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. Amsterdam: ELSEVIER SCIENCE BV, 2015, vol. 1852, No 5, p. 839-850. ISSN 0925-4439. Available from: https://dx.doi.org/10.1016/j.bbadis.2014.12.020.
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Basic information
Original name Fibroblast growth factor and canonical WNT/beta-catenin signaling cooperate in suppression of chondrocyte differentiation in experimental models of FGFR signaling in cartilage
Authors BUCHTOVÁ, marcela (203 Czech Republic, belonging to the institution), Veronika ORALOVÁ (203 Czech Republic), Anie AKLIAN (840 United States of America), Jan MAŠEK (203 Czech Republic, belonging to the institution), Iva VESELA (203 Czech Republic), Zhufeng OUYANG (840 United States of America), Tereza OBADALOVÁ (203 Czech Republic, belonging to the institution), Žaneta KONEČNÁ (203 Czech Republic, belonging to the institution), Tereza SPOUSTOVÁ (203 Czech Republic, belonging to the institution), Tereza POSPÍŠILOVÁ (203 Czech Republic, belonging to the institution), Petr MATULA (203 Czech Republic, belonging to the institution), Miroslav VAŘECHA (203 Czech Republic, belonging to the institution), Lukáš BÁLEK (203 Czech Republic, belonging to the institution), Iva GUDERNOVÁ (203 Czech Republic, belonging to the institution), Iva JELÍNKOVÁ (203 Czech Republic, belonging to the institution), Ivan DURAN (840 United States of America), Iveta ČERVENKOVÁ (703 Slovakia, belonging to the institution), Shunichi MURAKAMI (840 United States of America), Alois KOZUBÍK (203 Czech Republic, belonging to the institution), Petr DVOŘÁK (203 Czech Republic, belonging to the institution), Vítězslav BRYJA (203 Czech Republic, belonging to the institution) and Pavel KREJČÍ (203 Czech Republic, guarantor, belonging to the institution).
Edition Biochimica et Biophysica Acta - Molecular Basis of Disease, Amsterdam, ELSEVIER SCIENCE BV, 2015, 0925-4439.
Other information
Original language English
Type of outcome Article in a journal
Field of Study Genetics and molecular biology
Country of publisher Netherlands
Confidentiality degree is not subject to a state or trade secret
Impact factor Impact factor: 5.158
RIV identification code RIV/00216224:14110/15:00080765
Organization unit Faculty of Medicine
Doi http://dx.doi.org/10.1016/j.bbadis.2014.12.020
UT WoS 000353176200014
Keywords in English Cartilage; Chondrocyte; Differentiation; FGFR3; Fibroblast growth factor receptor; WNT
Tags EL OK, podil
Tags International impact, Reviewed
Changed by Changed by: Ing. Mgr. Věra Pospíšilíková, učo 9005. Changed: 10/7/2015 13:28.
Abstract
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.
Links
GA204/09/0498, research and development projectName: Dynamika proteinů interagujících s Dishevelled a jejich význam pro Wnt signálování
Investor: Czech Science Foundation, Dynamics of proteins interacting with Dishevelled and their importance for Wnt signalling
GBP302/12/G157, research and development projectName: Dynamika a organizace chromosomů během buněčného cyklu a při diferenciaci v normě a patologii
Investor: Czech Science Foundation
LH12004, research and development projectName: FGFR3-specifický adaptérom a jeho role v patologické FGFR3 signalizaci v nemoci (Acronym: AMVIS-FGFR3)
Investor: Ministry of Education, Youth and Sports of the CR
MUNI/A/0793/2012, interní kód MUName: Podpora výzkumné činnosti studentů v oblasti fyziologie a imunologie živočichů v roce 2013.
Investor: Masaryk University, Category A
MUNI/M/0071/2013, interní kód MUName: High-throughput screening of compound libraries aimed on discovery of novel inhibitors of the FGFR/ERK MAP kinase signaling (Acronym: HTS-FGFR)
Investor: Masaryk University, INTERDISCIPLINARY - Interdisciplinary research projects
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