title: Alteration of cartilage mechanical properties in absence of β1 integrins revealed by rheometry and FRAP analyses.
abstract: BACKGROUND
  Mechanical properties are essential for biological functions of the hyaline cartilage such as energy dissipation and diffusion of solutes. Mechanical properties are primarily dependent on the hierarchical organization of the two major extracellular matrix (ECM) macromolecular components of the cartilage: the fibrillar collagen network and the glycosaminoglycan (GAG)-substituted proteoglycan, mainly aggrecan, aggregates. Interaction of chondrocytes, the only cell type in the tissue, with the ECM through adhesion receptors is involved in establishing mechanical stability via bidirectional transduction of both mechanical forces and chemical signals. In this study, we aimed to determine the role of the transmembrane β1 integrin adhesion receptors in cartilage biomechanical properties by the use of genetic modification in mice.
  
  
  METHODS
  Costal cartilages of wild type and mutant mice lacking β1 integrins in chondrocytes were investigated. Cartilage compressive properties and solute diffusion were characterized by rheometric analysis and Fluorescence Recovery After Photobleaching (FRAP), respectively. Cartilage tissue sections were analyzed by histology, immunohistochemistry and transmission electron microscopy (TEM).
  
  
  RESULTS
  At the histological level, the mutant costal cartilage was characterized by chondrocyte rounding and loss of tissue polarity. Immunohistochemistry and safranin orange staining demonstrated apparently normal aggrecan and GAG levels, respectively. Antibody staining for collagen II and TEM showed comparable expression and organization of the collagen fibrils between mutant and control cartilages. Despite the lack of gross histological and ultrastructural abnormalities, rheological measurements revealed that the peak elastic modulus in compression of mutant cartilage was 1.6-fold higher than the peak elastic modulus of wild-type sample. Interestingly, the diffusion coefficient within the mutant cartilage tissue was found to be 1.2-fold lower in the extracellular space and 14-fold lower in the pericellular (PCM) space compared to control.
  
  
  CONCLUSIONS
  The results demonstrate that the absence of β1 integrins on the surface of chondrocytes increases the stiffness and modifies the diffusion properties of costal cartilage. Our data imply that β1 integrins-mediated chondrocyte-matrix interactions directly affect cartilage biomechanics probably by modifying physical properties of individual cells. This study thus highlights the crucial role of β1 integrins in the cartilage function.
authors.affiliation: Institut de Biologie et Chimie des Protéines, FRE3310 CNRS, Université de Lyon, 7 Passage du Vercors, F-69367 Lyon Cedex 07, France.
authors.forename: Carole
authors.initials: C
authors.lastname: Bougault
authors.forename: Livia
authors.initials: L
authors.lastname: Cueru
authors.forename: Jonathan
authors.initials: J
authors.lastname: Bariller
authors.forename: Marilyne
authors.initials: M
authors.lastname: Malbouyres
authors.forename: Anne
authors.initials: A
authors.lastname: Paumier
authors.forename: Attila
authors.initials: A
authors.lastname: Aszodi
authors.forename: Yves
authors.initials: Y
authors.lastname: Berthier
authors.forename: Frédéric
authors.initials: F
authors.lastname: Mallein-Gerin
authors.forename: Ana-Maria
authors.initials: AM
authors.lastname: Trunfio-Sfarghiu
mesh_terms: D000818:Animals; D002356:Cartilage / Q000502:physiology* / Q000648:ultrastructure; D019245:Compressive Strength; D004548:Elasticity; D005109:Extracellular Matrix / Q000648:ultrastructure; D036681:Fluorescence Recovery After Photobleaching; D019012:Integrin beta1 / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D046529:Microscopy, Electron, Transmission
chemical_list: D019012:Integrin beta1