title: Healthy and Osteoarthritic Synovial Fibroblasts Produce a Disintegrin and Metalloproteinase with Thrombospondin Motifs 4, 5, 7, and 12: Induction by IL-1β and Fibronectin and Contribution to Cartilage Damage.
abstract: Current description of osteoarthritis includes the involvement of synovial inflammation. Studies contributing to understanding the mechanisms of cross-talk and feedback among the joint tissues could be relevant to the development of therapies that block disease progression. During osteoarthritis, synovial fibroblasts exposed to anomalous mechanical forces and an inflammatory microenvironment release factors such as a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) metalloproteinases that mediate tissue damage and perpetuate inflammation. We therefore studied the production of ADAMTS by synovial fibroblasts and their contribution to cartilage degradation. Moreover, we analyzed the implication of two mediators present in the osteoarthritis joint, IL-1β as proinflammatory cytokine, and 45-kDa fibronectin fragments as products of matrix degradation. We reported that synovial fibroblasts constitutively express and release ADAMTS 4, 5, 7, and 12. Despite the contribution of both mediators to the stimulation of Runx2 and Wnt/β-catenin signaling pathways, as well as to ADAMTS expression, promoting the degradation of aggrecan and cartilage oligomeric matrix protein from cartilage, fibronectin fragments rather than IL-1β played the major pathological role in osteoarthritis, contributing to the maintenance of the disease. Moreover, higher levels of ADAMTS 4 and 7 and a specific regulation of ADAMTS-12 were observed in osteoarthritis, suggesting them as new potential therapeutic targets. Therefore, synovial fibroblasts provide the biochemical tools to the chronicity and destruction of the osteoarthritic joints.
authors.affiliation: Department of Cell Biology, Faculty of Biology, Complutense University of Madrid, Madrid, Spain.
authors.forename: Selene
authors.initials: S
authors.lastname: Pérez-García
authors.affiliation: Department of Cell Biology, Faculty of Biology, Complutense University of Madrid, Madrid, Spain.
authors.forename: Irene
authors.initials: I
authors.lastname: Gutiérrez-Cañas
authors.affiliation: Department of Cell Biology, Faculty of Biology, Complutense University of Madrid, Madrid, Spain.
authors.forename: Iria V
authors.initials: IV
authors.lastname: Seoane
authors.affiliation: Traumatology Service, Hospital Universitario de La Princesa, Medical Research Institute, Madrid, Spain.
authors.forename: Julián
authors.initials: J
authors.lastname: Fernández
authors.affiliation: Department of Immunology and Oncology, Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas (CSIC), Madrid, Spain.
authors.forename: Mario
authors.initials: M
authors.lastname: Mellado
authors.affiliation: Department of Cell Biology, Faculty of Biology, Complutense University of Madrid, Madrid, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Leceta
authors.affiliation: Cellular Inflammation and Cartilage Research Group, Hospital del Mar Research Institute (IMIM), Barcelona, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Tío
authors.affiliation: Department of Cell Biology, Faculty of Biology, Complutense University of Madrid, Madrid, Spain.
authors.forename: Raúl
authors.initials: R
authors.lastname: Villanueva-Romero
authors.affiliation: Department of Cell Biology, Faculty of Biology, Complutense University of Madrid, Madrid, Spain.
authors.forename: Yasmina
authors.initials: Y
authors.lastname: Juarranz
authors.affiliation: Department of Cell Biology, Faculty of Biology, Complutense University of Madrid, Madrid, Spain. Electronic address: gomariz@bio.ucm.es.
authors.forename: Rosa P
authors.initials: RP
authors.lastname: Gomariz
mesh_terms: D000071096:ADAMTS Proteins / Q000096:biosynthesis*; D000368:Aged; D000369:Aged, 80 and over; D015153:Blotting, Western; D002358:Cartilage, Articular / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005347:Fibroblasts / Q000378:metabolism*; D005353:Fibronectins / Q000378:metabolism*; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010003:Osteoarthritis / Q000378:metabolism / Q000473:pathology*; D016133:Polymerase Chain Reaction; D013583:Synovial Membrane / Q000378:metabolism / Q000473:pathology
chemical_list: D005353:Fibronectins; D053583:Interleukin-1beta; D000071096:ADAMTS Proteins