Fibroblast growth factor and canonical WNT/β-catenin signaling cooperate in suppression of chondrocyte differentiation in experimental models of FGFR signaling in cartilage
Jazyk angličtina Země Nizozemsko Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
25558817
DOI
10.1016/j.bbadis.2014.12.020
PII: S0925-4439(14)00414-1
Knihovny.cz E-zdroje
- Klíčová slova
- Cartilage, Chondrocyte, Differentiation, FGFR3, Fibroblast growth factor receptor, WNT,
- MeSH
- beta-katenin genetika metabolismus MeSH
- biologické modely MeSH
- buněčná diferenciace účinky léků genetika MeSH
- chondrocyty účinky léků metabolismus MeSH
- chrupavka cytologie účinky léků metabolismus MeSH
- fibroblastové růstové faktory farmakologie MeSH
- fibroblastový růstový faktor 2 farmakologie MeSH
- HEK293 buňky MeSH
- končetinové pupeny účinky léků embryologie metabolismus MeSH
- konfokální mikroskopie MeSH
- krysa rodu Rattus MeSH
- kultivované buňky MeSH
- LDL receptor related protein 6 genetika metabolismus MeSH
- lidé MeSH
- nádorové buněčné linie MeSH
- polymerázová řetězová reakce s reverzní transkripcí MeSH
- protein Wnt3A farmakologie MeSH
- proteiny Wnt genetika metabolismus farmakologie MeSH
- receptory fibroblastových růstových faktorů genetika metabolismus MeSH
- signální transdukce účinky léků genetika MeSH
- synergismus léků MeSH
- transkriptom účinky léků genetika MeSH
- western blotting MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- beta-katenin MeSH
- fibroblastové růstové faktory MeSH
- fibroblastový růstový faktor 2 MeSH
- LDL receptor related protein 6 MeSH
- Lrp6 protein, mouse MeSH Prohlížeč
- protein Wnt3A MeSH
- proteiny Wnt MeSH
- receptory fibroblastových růstových faktorů MeSH
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/β-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/β-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/β-catenin in suppression of chondrocyte differentiation.
Centre for Biomedical Image Analysis Faculty of Informatics Masaryk University Brno Czech Republic
Department of Biology Faculty of Medicine Masaryk University Brno Czech Republic
Department of Orthopaedic Surgery David Geffen School of Medicine at UCLA Los Angeles CA USA
Department of Orthopaedics Case Western Reserve University Cleveland OH USA
Institute of Animal Physiology and Genetics AS CR v v i Brno Czech Republic
Institute of Experimental Biology Faculty of Sciences Masaryk University Brno Czech Republic
Medical Genetics Institute Cedars Sinai Medical Center Los Angeles CA USA
Citace poskytuje Crossref.org
A registry of achondroplasia: a 6-year experience from the Czechia and Slovak Republic
One reporter for in-cell activity profiling of majority of protein kinase oncogenes
