title: Synovial fibroblasts spread rheumatoid arthritis to unaffected joints.
abstract: Active rheumatoid arthritis originates from few joints but subsequently affects the majority of joints. Thus far, the pathways of the progression of the disease are largely unknown. As rheumatoid arthritis synovial fibroblasts (RASFs) which can be found in RA synovium are key players in joint destruction and are able to migrate in vitro, we evaluated the potential of RASFs to spread the disease in vivo. To simulate the primary joint of origin, we implanted healthy human cartilage together with RASFs subcutaneously into severe combined immunodeficient (SCID) mice. At the contralateral flank, we implanted healthy cartilage without cells. RASFs showed an active movement to the naive cartilage via the vasculature independent of the site of application of RASFs into the SCID mouse, leading to a marked destruction of the target cartilage. These findings support the hypothesis that the characteristic clinical phenomenon of destructive arthritis spreading between joints is mediated, at least in part, by the transmigration of activated RASFs.
authors.affiliation: Department of Internal Medicine and Rheumatology, Justus-Liebig-University Giessen, Kerckhoff-Clinic, Bad Nauheim, Germany.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Lefèvre
authors.forename: Anette
authors.initials: A
authors.lastname: Knedla
authors.forename: Christoph
authors.initials: C
authors.lastname: Tennie
authors.forename: Andreas
authors.initials: A
authors.lastname: Kampmann
authors.forename: Christina
authors.initials: C
authors.lastname: Wunrau
authors.forename: Robert
authors.initials: R
authors.lastname: Dinser
authors.forename: Adelheid
authors.initials: A
authors.lastname: Korb
authors.forename: Eva-Maria
authors.initials: EM
authors.lastname: Schnäker
authors.forename: Ingo H
authors.initials: IH
authors.lastname: Tarner
authors.forename: Paul D
authors.initials: PD
authors.lastname: Robbins
authors.forename: Christopher H
authors.initials: CH
authors.lastname: Evans
authors.forename: Henning
authors.initials: H
authors.lastname: Stürz
authors.forename: Jürgen
authors.initials: J
authors.lastname: Steinmeyer
authors.forename: Steffen
authors.initials: S
authors.lastname: Gay
authors.forename: Jürgen
authors.initials: J
authors.lastname: Schölmerich
authors.forename: Thomas
authors.initials: T
authors.lastname: Pap
authors.forename: Ulf
authors.initials: U
authors.lastname: Müller-Ladner
authors.forename: Elena
authors.initials: E
authors.lastname: Neumann
mesh_terms: D000818:Animals; D001172:Arthritis, Rheumatoid / Q000473:pathology*; D002356:Cartilage / Q000473:pathology / Q000503:physiopathology; D002448:Cell Adhesion; D002465:Cell Movement; D018450:Disease Progression; D005109:Extracellular Matrix; D005347:Fibroblasts / Q000473:pathology; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D013583:Synovial Membrane / Q000473:pathology* / Q000503:physiopathology; D014183:Transplantation, Heterologous