title: Integrin alpha1beta1 mediates collagen induction of MMP-13 expression in MC615 chondrocytes.
abstract: During endochondral ossification, type I collagen is synthesized by osteoblasts together with some hypertrophic chondrocytes. Type I collagen has also been reported to be progressively synthesized in degenerative joints. Because Matrix Metalloproteinase-13 (MMP-13) plays an active role in remodeling cartilage in fetal development and osteoarthritic cartilage, we investigated whether type I collagen could activate MMP-13 expression in chondrocytes. We used a well-established chondrocytic cell line (MC615) and we found that MMP-13 expression was induced in MC615 cells cultured in type I collagen gel. We also found that alpha1beta1 integrin, a major collagen receptor, was expressed by MC615 cells and we further assessed the role of alpha1beta1 integrin in conducting MMP-13 expression. Induction of MMP-13 expression by collagen was potently and synergistically inhibited by blocking antibodies against alpha1 and beta1 integrin subunits, indicating that alpha1beta1 integrin mediates the MMP-13-inducing cellular signal generated by three-dimensional type I collagen. We also determined that activities of tyrosine kinase and ERK and JNK MAP kinases were required for this collagen-induced MMP-13 expression. Interestingly, bone morphogenetic protein (BMP)-2 opposed this induction, an effect that may be related to a role of BMP-2 in the maintenance of cartilage matrix.
authors.affiliation: Laboratoire de Biologie et Ingénierie du Cartilage, Institut de Biologie et Chimie des Protéines, UMR 5086 CNRS/UCBL, IFR 128 BioSciences Lyon-Gerland, 7 passage du Vercors, 69367 Lyon Cedex 07, France.
authors.forename: Marie-Claire
authors.initials: MC
authors.lastname: Ronzière
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Aubert-Foucher
authors.forename: Jérôme
authors.initials: J
authors.lastname: Gouttenoire
authors.forename: Janine
authors.initials: J
authors.lastname: Bernaud
authors.forename: Daniel
authors.initials: D
authors.lastname: Herbage
authors.forename: Frédéric
authors.initials: F
authors.lastname: Mallein-Gerin
mesh_terms: D000818:Animals; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000378:metabolism / Q000494:pharmacology; D002460:Cell Line; D019902:Chondrocytes / Q000187:drug effects / Q000378:metabolism*; D024042:Collagen Type I / Q000378:metabolism*; D017364:Collagenases / Q000235:genetics / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005786:Gene Expression Regulation; D039222:Integrin alpha1beta1 / Q000235:genetics / Q000378:metabolism*; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D053509:Matrix Metalloproteinase 13; D051379:Mice; D019000:Phosphotyrosine / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000378:metabolism / Q000494:pharmacology
chemical_list: C525719:Bmp2 protein, mouse; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D024042:Collagen Type I; D039222:Integrin alpha1beta1; D016212:Transforming Growth Factor beta; D019000:Phosphotyrosine; D011505:Protein-Tyrosine Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D017364:Collagenases; D053509:Matrix Metalloproteinase 13; C507081:Mmp13 protein, mouse