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

J 2015

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

BUCHTOVÁ, marcela, Veronika ORALOVÁ, Anie AKLIAN, Jan MAŠEK, Iva VESELA et. al.

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

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

Genetics and molecular biology

Country of publisher

Netherlands

Confidentiality degree

není předmětem státního či obchodního tajemství

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

Abstract

V originále

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 project

Name: 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 project

Name: Dynamika a organizace chromosomů během buněčného cyklu a při diferenciaci v normě a patologii

Investor: Czech Science Foundation

LH12004, research and development project

Name: 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 MU

Name: Podpora výzkumné činnosti studentů v oblasti fyziologie a imunologie živočichů v roce 2013.

Investor: Masaryk University, Category A

MUNI/M/0071/2013, interní kód MU

Name: 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

Citovat

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.

@article{1298521,
   author = {Buchtová, marcela and Oralová, Veronika and Aklian, Anie and Mašek, Jan and Vesela, Iva and Ouyang, Zhufeng and Obadalová, Tereza and Konečná, Žaneta and Spoustová, Tereza and Pospíšilová, Tereza and Matula, Petr and Vařecha, Miroslav and Bálek, Lukáš and Gudernová, Iva and Jelínková, Iva and Duran, Ivan and Červenková, Iveta and Murakami, Shunichi and Kozubík, Alois and Dvořák, Petr and Bryja, Vítězslav and Krejčí, Pavel},
   article_location = {Amsterdam},
   article_number = {5},
   doi = {http://dx.doi.org/10.1016/j.bbadis.2014.12.020},
   keywords = {Cartilage; Chondrocyte; Differentiation; FGFR3; Fibroblast growth factor receptor; WNT},
   language = {eng},
   issn = {0925-4439},
   journal = {Biochimica et Biophysica Acta - Molecular Basis of Disease},
   title = {Fibroblast growth factor and canonical WNT/beta-catenin signaling cooperate in suppression of chondrocyte differentiation in experimental models of FGFR signaling in cartilage},
   volume = {1852},
   year = {2015}
}

TY  - JOUR
ID  - 1298521
AU  - Buchtová, marcela - Oralová, Veronika - Aklian, Anie - Mašek, Jan - Vesela, Iva - Ouyang, Zhufeng - Obadalová, Tereza - Konečná, Žaneta - Spoustová, Tereza - Pospíšilová, Tereza - Matula, Petr - Vařecha, Miroslav - Bálek, Lukáš - Gudernová, Iva - Jelínková, Iva - Duran, Ivan - Červenková, Iveta - Murakami, Shunichi - Kozubík, Alois - Dvořák, Petr - Bryja, Vítězslav - Krejčí, Pavel
PY  - 2015
TI  - Fibroblast growth factor and canonical WNT/beta-catenin signaling cooperate in suppression of chondrocyte differentiation in experimental models of FGFR signaling in cartilage
JF  - Biochimica et Biophysica Acta - Molecular Basis of Disease
VL  - 1852
IS  - 5
SP  - 839-850
EP  - 839-850
PB  - ELSEVIER SCIENCE BV
SN  - 09254439
KW  - Cartilage
KW  - Chondrocyte
KW  - Differentiation
KW  - FGFR3
KW  - Fibroblast growth factor receptor
KW  - WNT
N2  - 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.
ER  -

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. \textit{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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