title: FGF, TGFβ and Wnt crosstalk: embryonic to in vitro cartilage development from mesenchymal stem cells.
abstract: Articular cartilage is easily damaged, yet difficult to repair. Cartilage tissue engineering seems a promising therapeutic solution to restore articular cartilage structure and function, with mesenchymal stem cells (MSCs) receiving increasing attention for their promise to promote cartilage repair. It is known from embryology that members of the fibroblast growth factor (FGF), transforming growth factor-β (TGFβ) and wingless-type (Wnt) protein families are involved in controlling different differentiation stages during chondrogenesis. Individually, these pathways have been extensively studied but so far attempts to recapitulate embryonic development in in vitro MSC chondrogenesis have failed to produce stable and functioning articular cartilage; instead, transient hypertrophic cartilage is obtained. We believe a better understanding of the simultaneous integration of these factors will improve how we relate embryonic chondrogenesis to in vitro MSC chondrogenesis. This narrative review attempts to define current knowledge on the crosstalk between the FGF, TGFβ and Wnt signalling pathways during different stages of mesenchymal chondrogenesis. Connecting embryogenesis and in vitro differentiation of human MSCs might provide insights into how to improve and progress cartilage tissue engineering for the future.
authors.affiliation: Department of Orthopaedics, Erasmus MC, University Medical Centre, Dr. Molewaterplein 50, 3015 GE, Rotterdam, The Netherlands; School of Veterinary Medicine, Veterinary Science Centre, University College Dublin, Belfield, Dublin 4, Ireland.
authors.forename: Mairéad A
authors.initials: MA
authors.lastname: Cleary
authors.forename: Gerjo J V M
authors.initials: GJ
authors.lastname: van Osch
authors.forename: Pieter A
authors.initials: PA
authors.lastname: Brama
authors.forename: Catharine A
authors.initials: CA
authors.lastname: Hellingman
authors.forename: Roberto
authors.initials: R
authors.lastname: Narcisi
mesh_terms: D000818:Animals; D002356:Cartilage / Q000378:metabolism*; D020219:Chondrogenesis; D004622:Embryo, Mammalian / Q000378:metabolism*; D005346:Fibroblast Growth Factors / Q000378:metabolism*; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D051153:Wnt Proteins / Q000378:metabolism*; D060449:Wnt Signaling Pathway
chemical_list: D016212:Transforming Growth Factor beta; D051153:Wnt Proteins; D005346:Fibroblast Growth Factors
keywords: cell differentiation; cell signalling; chondrogenesis; fibroblast growth factor; mesenchymal stem cell; transforming growth factor-β; wingless-type protein