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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Arthritis+Res+Ther
2016 ; 18
(1
): 270
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Rheumatoid synovial fibroblasts differentiate into distinct subsets in the
presence of cytokines and cartilage
#MMPMID27863512
Croft AP
; Naylor AJ
; Marshall JL
; Hardie DL
; Zimmermann B
; Turner J
; Desanti G
; Adams H
; Yemm AI
; Müller-Ladner U
; Dayer JM
; Neumann E
; Filer A
; Buckley CD
Arthritis Res Ther
2016[Nov]; 18
(1
): 270
PMID27863512
show ga
BACKGROUND: We investigated two distinct synovial fibroblast populations that
were located preferentially in the lining or sub-lining layers and defined by
their expression of either podoplanin (PDPN) or CD248, and explored their ability
to undergo self-assembly and transmigration in vivo. METHODS: Synovial
fibroblasts (SF) were cultured in vitro and phenotypic changes following
stimulation with interleukin (IL)-1?, tumor necrosis factor (TNF)-?, and
transforming growth factor (TGF)-?1 were examined. To examine the phenotype of SF
in vivo, a severe combined immunodeficiency (SCID) human-mouse model of cartilage
destruction was utilised. RESULTS: SF in the lining layer in rheumatoid arthritis
(RA) expressed high levels of PDPN compared to the normal synovium, whereas CD248
expression was restricted to sub-lining layer cells. TNF-? or IL1 stimulation in
vitro resulted in an increased expression of PDPN. In contrast, stimulation with
TGF-?1 induced CD248 expression. In the SCID human-mouse model, rheumatoid SF
recapitulated the expression of PDPN and CD248. Fibroblasts adjacent to cartilage
expressed PDPN, and attached to, invaded, and degraded cartilage. PDPN(+)
CD248(-) SF preceded the appearance of PDPN(-) CD248(+) cells in contralateral
implants. CONCLUSIONS: We have identified two distinct SF populations identified
by expression of either PDPN or CD248 which are located within different
anatomical compartments of the inflamed synovial membrane. These markers
discriminate between SF subsets with distinct biological properties. As
PDPN-expressing cells are associated with early fibroblast migration and
cartilage erosion in vivo, we propose that PDPN-expressing cells may be an
attractive therapeutic target in RA.