title: Inhibition of oncostatin M in osteoarthritic synovial fluid enhances GAG production in osteoarthritic cartilage repair.
abstract: Mediators in the synovial fluid are thought to play a major role in osteoarthritic cartilage turnover. The purpose of the current study was to investigate the role of oncostatin M (OSM) in osteoarthritis (OA) by evaluating the presence of the cytokine and its receptors in the OA joint and interfering with its activity in synovial fluid co-cultured with cartilage explants. OSM levels were increased in the synovial fluid of osteoarthritic patients compared to healthy donors. Immunohistochemistry confirmed the presence of both the leukaemia inhibitory factor (LIF) and OSM receptors for OSM throughout the whole depth of osteoarthritic cartilage and synovial tissue, whereas in healthy cartilage their presence seemed more restricted to the superficial zone. Blocking OSM activity, using an activity inhibiting antibody, in 25 % osteoarthritic synovial fluid added to OA cartilage explant cultures increased glycosaminoglycan (GAG) content from 18.6 mg/g to 24.3 mg/g (P < 0.03) and total production from 7.0 mg/g to 11.9 mg/g (P < 0.003). However, OSM exogenously added to cartilage explant cultures reflecting low and high concentrations in the synovial fluid (5 and 50 pg/mL) did not affect cartilage matrix turnover, suggesting that factors present in the synovial fluid act in concert with OSM to inhibit GAG production. The current study indicates the potential to enhance cartilage repair in osteoarthritis by modulating the joint environment by interfering with OSM activity.
authors.affiliation: Department of Orthopaedics, University Medical Centre Utrecht, Heidelberglaan 100, PO Box 85090, 3508AB Utrecht, The Netherlands.l.b.creemers@umcutrecht.nl.
authors.forename: Michiel
authors.initials: M
authors.lastname: Beekhuizen
authors.forename: Gerjo J V M
authors.initials: GJ
authors.lastname: van Osch
authors.forename: Arjan G J
authors.initials: AG
authors.lastname: Bot
authors.forename: Myrthe C L
authors.initials: MC
authors.lastname: Hoekstra
authors.forename: Daniel B F
authors.initials: DB
authors.lastname: Saris
authors.forename: Wouter J A
authors.initials: WJ
authors.lastname: Dhert
authors.forename: Laura B
authors.initials: LB
authors.lastname: Creemers
mesh_terms: D019138:Antibodies, Blocking / Q000494:pharmacology; D002356:Cartilage / Q000378:metabolism*; D016022:Case-Control Studies; D006025:Glycosaminoglycans / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D053683:Oncostatin M / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D010003:Osteoarthritis / Q000378:metabolism*; D013582:Synovial Fluid / Q000378:metabolism*
chemical_list: D019138:Antibodies, Blocking; D006025:Glycosaminoglycans; C020341:glucosaminoglycans; D053683:Oncostatin M