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.

Základní údaje

Originální název

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

Autoři

Vydání

Biochimica et Biophysica Acta - Molecular Basis of Disease, Amsterdam, ELSEVIER SCIENCE BV, 2015, 0925-4439

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

Genetika a molekulární biologie

Stát vydavatele

Nizozemské království

Utajení

není předmětem státního či obchodního tajemství

Impakt faktor

Impact factor: 5.158

Kód RIV

RIV/00216224:14110/15:00080765

Organizační jednotka

Lékařská fakulta

DOI

https://doi.org/10.1016/j.bbadis.2014.12.020

UT WoS

000353176200014

EID Scopus

2-s2.0-84922439626

Klíčová slova anglicky

Cartilage; Chondrocyte; Differentiation; FGFR3; Fibroblast growth factor receptor; WNT

Štítky

EL OK, podil

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 10. 7. 2015 13:28, Ing. Mgr. Věra Pospíšilíková

Anotace

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.

Návaznosti

GA204/09/0498, projekt VaV

Název: Dynamika proteinů interagujících s Dishevelled a jejich význam pro Wnt signálování

Investor: Grantová agentura ČR, Dynamika proteinů interagujících s Dishevelled a jejich význam pro Wnt signálování

GBP302/12/G157, projekt VaV

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

Investor: Grantová agentura ČR, Dynamika a organizace chromosomů během buněčného cyklu a při diferenciaci v normě a patologii

LH12004, projekt VaV

Název: FGFR3-specifický adaptérom a jeho role v patologické FGFR3 signalizaci v nemoci (Akronym: AMVIS-FGFR3)

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, FGFR3-specifický adaptérom a jeho role v patologické FGFR3 signalizaci v nemoci

MUNI/A/0793/2012, interní kód MU

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

Investor: Masarykova univerzita, Podpora výzkumné činnosti studentů v oblasti fyziologie a imunologie živočichů v roce 2013., DO R. 2020_Kategorie A - Specifický výzkum - Studentské výzkumné projekty

MUNI/M/0071/2013, interní kód MU

Název: High-throughput screening of compound libraries aimed on discovery of novel inhibitors of the FGFR/ERK MAP kinase signaling (Akronym: HTS-FGFR)

Investor: Masarykova univerzita, High-throughput screening of compound libraries aimed on discovery of novel inhibitors of the FGFR/ERK MAP kinase signaling, INTERDISCIPLINARY - Mezioborové výzkumné projekty

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 a 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, roč. 1852, č. 5, s. 839-850. ISSN 0925-4439. Dostupné z: https://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 = {https://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 a 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, roč.~1852, č.~5, s.~839-850. ISSN~0925-4439. Dostupné z: https://doi.org/10.1016/j.bbadis.2014.12.020.

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