Synovial fibroblasts spread rheumatoid arthritis to unaffected joints.
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.
Lefèvre
Stephanie
S
Department of Internal Medicine and Rheumatology, Justus-Liebig-University Giessen, Kerckhoff-Clinic, Bad Nauheim, Germany.
Knedla
Anette
A
Tennie
Christoph
C
Kampmann
Andreas
A
Wunrau
Christina
C
Dinser
Robert
R
Korb
Adelheid
A
Schnäker
Eva-Maria
EM
Tarner
Ingo H
IH
Robbins
Paul D
PD
Evans
Christopher H
CH
Stürz
Henning
H
Steinmeyer
Jürgen
J
Gay
Steffen
S
Schölmerich
Jürgen
J
Pap
Thomas
T
Müller-Ladner
Ulf
U
Neumann
Elena
E
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