Matrilin-3 switches from anti- to pro-anabolic upon integration to the extracellular matrix

Autor: Jean-Baptiste Vincourt, Didier Mainard, Patrick Netter, Claudie Bantsimba-Malanda, Justine Cottet, Laurent Grossin, Virginie Libante, Pierre Gillet, Stéphanie Etienne, Jacques Magdalou
Přispěvatelé: Ingénierie Moléculaire et Physiopathologie Articulaire (IMoPA), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Dynamique des Génomes et Adaptation Microbienne (DynAMic), Université de Lorraine (UL)-Institut National de la Recherche Agronomique (INRA), Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL)
Jazyk: angličtina
Rok vydání: 2012
Předmět:
Cartilage
Articular
Male
Integrin
Primary Cell Culture
Cartilage metabolism
[SDV.BC]Life Sciences [q-bio]/Cellular Biology
[SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC]
Matrix (biology)
Chondrocyte
Extracellular matrix
Transforming Growth Factor beta1
03 medical and health sciences
0302 clinical medicine
Chondrocytes
Osteoarthritis
Synovial Fluid
medicine
Cell Adhesion
Humans
Matrilin Proteins
RNA
Messenger
Phosphorylation
Molecular Biology
Collagen Type II
ComputingMilieux_MISCELLANEOUS
030304 developmental biology
Aged
0303 health sciences
Extracellular Matrix Proteins
biology
Dose-Response Relationship
Drug
Chemistry
Cartilage homeostasis
Cartilage
Recombinant Proteins
Cell biology
Extracellular Matrix
Protein Structure
Tertiary
Protein Transport
medicine.anatomical_structure
Biochemistry
Solubility
030220 oncology & carcinogenesis
biology.protein
Female
Signal transduction
Integrin alpha5beta1
Signal Transduction
Zdroj: Matrix Biology
Matrix Biology, Elsevier, 2012, 31 (5), pp.290-298. ⟨10.1016/j.matbio.2012.03.004⟩
ISSN: 0945-053X
DOI: 10.1016/j.matbio.2012.03.004⟩
Popis: The extracellular matrix (ECM) has long been viewed primarily as an organized network of solid-phase ligands for integrin receptors. During degenerative processes, such as osteoarthritis, the ECM undergoes deterioration, resulting in its remodeling and in the release of some of its components. Matrilin-3 (MATN3) is an almost cartilage specific, pericellular protein acting in the assembly of the ECM of chondrocytes. In the past, MATN3 was found required for cartilage homeostasis, but also involved in osteoarthritis-related pro-catabolic functions. Here, to better understand the pathological and physiological functions of MATN3, its concentration as a circulating protein in articular fluids of human osteoarthritic patients was determined and its functions as a recombinant protein produced in human cells were investigated with particular emphasis on the physical state under which it is presented to chondrocytes. MATN3 down-regulated cartilage extracellular matrix (ECM) synthesis and up-regulated catabolism when administered as a soluble protein. When artificially immobilized, however, MATN3 induced chondrocyte adhesion via a α5β1 integrin-dependent mechanism, AKT activation and favored survival and ECM synthesis. Furthermore, MATN3 bound directly to isolated α5β1 integrin in vitro. TGFβ1 stimulation of chondrocytes allowed integration of exogenous MATN3 into their ECM and ECM-integrated MATN3 induced AKT phosphorylation and improved ECM synthesis and accumulation. In conclusion, the integration of MATN3 to the pericellular matrix of chondrocytes critically determines the direction toward which MATN3 regulates cartilage metabolism. These data explain how MATN3 plays either beneficial or detrimental functions in cartilage and highlight the important role played by the physical state of ECM molecules.
Databáze: OpenAIRE
Externí odkaz: