title: Cartilage tissue engineering: molecular control of chondrocyte differentiation for proper cartilage matrix reconstruction.
abstract: BACKGROUND
  Articular cartilage defects are a veritable therapeutic problem because therapeutic options are very scarce. Due to the poor self-regeneration capacity of cartilage, minor cartilage defects often lead to osteoarthritis. Several surgical strategies have been developed to repair damaged cartilage. Autologous chondrocyte implantation (ACI) gives encouraging results, but this cell-based therapy involves a step of chondrocyte expansion in a monolayer, which results in the loss in the differentiated phenotype. Thus, despite improvement in the quality of life for patients, reconstructed cartilage is in fact fibrocartilage. Successful ACI, according to the particular physiology of chondrocytes in vitro, requires active and phenotypically stabilized chondrocytes.
  
  
  METHODS
  This review describes the unique physiology of cartilage, with the factors involved in its formation, stabilization and degradation. Then, we focus on some of the most recent advances in cell therapy and tissue engineering that open up interesting perspectives for maintaining or obtaining the chondrogenic character of cells in order to treat cartilage lesions.
  
  
  CONCLUSIONS
  Current research involves the use of chondrocytes or progenitor stem cells, associated with "smart" biomaterials and growth factors. Other influential factors, such as cell sources, oxygen pressure and mechanical strain are considered, as are recent developments in gene therapy to control the chondrocyte differentiation/dedifferentiation process.
  
  
  CONCLUSIONS
  This review provides new information on the mechanisms regulating the state of differentiation of chondrocytes and the chondrogenesis of mesenchymal stem cells that will lead to the development of new restorative cell therapy approaches in humans. This article is part of a Special Issue entitled Matrix-mediated cell behaviour and properties.
authors.affiliation: Laboratoire Microenvironnement Cellulaire et Pathologies (MILPAT) EA 4652, SFR 146 ICORE, Faculty of Medicine, IBFA, University of Caen/Lower-Normandy (UCLN), France.
authors.forename: Magali
authors.initials: M
authors.lastname: Demoor
authors.affiliation: Laboratoire Microenvironnement Cellulaire et Pathologies (MILPAT) EA 4652, SFR 146 ICORE, Faculty of Medicine, IBFA, University of Caen/Lower-Normandy (UCLN), France.
authors.forename: David
authors.initials: D
authors.lastname: Ollitrault
authors.affiliation: Laboratoire Microenvironnement Cellulaire et Pathologies (MILPAT) EA 4652, SFR 146 ICORE, Faculty of Medicine, IBFA, University of Caen/Lower-Normandy (UCLN), France.
authors.forename: Tangni
authors.initials: T
authors.lastname: Gomez-Leduc
authors.affiliation: Laboratoire Microenvironnement Cellulaire et Pathologies (MILPAT) EA 4652, SFR 146 ICORE, Faculty of Medicine, IBFA, University of Caen/Lower-Normandy (UCLN), France.
authors.forename: Mouloud
authors.initials: M
authors.lastname: Bouyoucef
authors.affiliation: Laboratoire Microenvironnement Cellulaire et Pathologies (MILPAT) EA 4652, SFR 146 ICORE, Faculty of Medicine, IBFA, University of Caen/Lower-Normandy (UCLN), France.
authors.forename: Magalie
authors.initials: M
authors.lastname: Hervieu
authors.affiliation: Laboratory of Biology and Engineering of Cartilage, UMR 5305 CNRS-Univ. de Lyon, IBCP, Lyon, France.
authors.forename: Hugo
authors.initials: H
authors.lastname: Fabre
authors.affiliation: Laboratory of Biology and Engineering of Cartilage, UMR 5305 CNRS-Univ. de Lyon, IBCP, Lyon, France.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Lafont
authors.affiliation: CIRALE (Centre d'imagerie et de recherche sur les affections locomotrices), USC INRA-ENVA (Ecole Nationale Vétérinaire d'Alfort) 957, Equipe Biomécanique et pathologie locomotrice du cheval), Imagerie et Pathologie Ostéo-Articulaire, University of Caen/Lower-Normandy, Goustranville, France.
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Denoix
authors.affiliation: CIRALE (Centre d'imagerie et de recherche sur les affections locomotrices), USC INRA-ENVA (Ecole Nationale Vétérinaire d'Alfort) 957, Equipe Biomécanique et pathologie locomotrice du cheval), Imagerie et Pathologie Ostéo-Articulaire, University of Caen/Lower-Normandy, Goustranville, France.
authors.forename: Fabrice
authors.initials: F
authors.lastname: Audigié
authors.affiliation: Laboratory of Biology and Engineering of Cartilage, UMR 5305 CNRS-Univ. de Lyon, IBCP, Lyon, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Mallein-Gerin
authors.affiliation: Laboratoire Microenvironnement Cellulaire et Pathologies (MILPAT) EA 4652, SFR 146 ICORE, Faculty of Medicine, IBFA, University of Caen/Lower-Normandy (UCLN), France.
authors.forename: Florence
authors.initials: F
authors.lastname: Legendre
authors.affiliation: Laboratoire Microenvironnement Cellulaire et Pathologies (MILPAT) EA 4652, SFR 146 ICORE, Faculty of Medicine, IBFA, University of Caen/Lower-Normandy (UCLN), France. Electronic address: philippe.galera@unicaen.fr.
authors.forename: Philippe
authors.initials: P
authors.lastname: Galera
mesh_terms: D000818:Animals; D002358:Cartilage, Articular / Q000166:cytology / Q000502:physiology*; D002454:Cell Differentiation; D019902:Chondrocytes / Q000166:cytology* / Q000637:transplantation; D020219:Chondrogenesis; D005109:Extracellular Matrix / Q000378:metabolism*; D006801:Humans; D023822:Tissue Engineering
keywords: Cartilage; Cell therapy; Chondrocyte; Mesenchymal stem cell; Osteoarthritis; Tissue engineering