Fibroblast growth factor and canonical WNT/β-catenin signaling cooperate in suppression of chondrocyte differentiation in experimental models of FGFR signaling in cartilage
Autor: | Iva Vesela, Petr Dvorak, Miroslav Varecha, Vitezslav Bryja, Iveta Cervenkova, Alois Kozubík, Marcela Buchtová, Iva Jelínková, Anie Aklian, Petr Matula, Zaneta Konecna, Tereza Spoustova, Pavel Krejci, Tereza Pospisilova, Ivan Duran, Tereza Obadalova, Lukas Balek, Iva Gudernova, Shunichi Murakami, Veronika Oralova, Jan Masek, Zhufeng Ouyang |
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Rok vydání: | 2015 |
Předmět: |
RHOA
Fibroblast growth factor 0302 clinical medicine Cells Cultured beta Catenin 0303 health sciences Microscopy Confocal biology Reverse Transcriptase Polymerase Chain Reaction Chemistry Wnt signaling pathway LRP6 Cell Differentiation Drug Synergism LRP5 Fibroblast growth factor receptor Cell biology medicine.anatomical_structure Low Density Lipoprotein Receptor-Related Protein-6 Differentiation Molecular Medicine Fibroblast Growth Factor 2 Signal Transduction medicine.medical_specialty Limb Buds Blotting Western Models Biological Chondrocyte WNT 03 medical and health sciences Limb bud Chondrocytes Cell Line Tumor Wnt3A Protein Internal medicine medicine Animals Humans Molecular Biology 030304 developmental biology Receptors Fibroblast Growth Factor Rats Fibroblast Growth Factors Wnt Proteins HEK293 Cells Cartilage Endocrinology FGFR3 biology.protein Transcriptome 030217 neurology & neurosurgery |
Zdroj: | Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease. 1852:839-850 |
ISSN: | 0925-4439 |
Popis: | 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. |
Databáze: | OpenAIRE |
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