ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 1969

Neurotrophin Receptor p75 (CD271) Defines a Distinct Synovial Fibroblast Subset in Rheumatoid and Osteoarthritic Synovial Tissues with Enhanced Proinflammatory Potential

Manuel J. Del Rey1, Regina Faré1, Gabriel Criado2, Alicia Usategui1, Vanessa Miranda1, Juan D. Cañete3 and Jose L. Pablos1, 1Servicio de Reumatología, Instituto de Investigación Hospital 12 de Octubre (I+12), Madrid, Spain, 2Grupo de Enfermedades Inflamatorias y Autoinmunes, Instituto de Investigación Hospital 12 de Octubre (I+12), Madrid, Spain, 3Arthritis Unit. Rheumatology Department, Hospital Clínic of Barcelona, Barcelona, Spain

Meeting: 2014 ACR/ARHP Annual Meeting

Keywords: , , , ,

Session Information

Title: Cytokines, Mediators, Cell-cell Adhesion, Cell Trafficking and Angiogenesis

Session Type: Abstract Submissions (ACR)

Background/Purpose

Synovial mesenchynmal or stromal cells constitute a heterogeneous cell population difficult to characterize ex vivo due to a paucity of cell markers and are usually named synovial fibroblasts (SF). CD271, the low affinity receptor for neurotrophin nerve growth factor (NGF), is considered a mesenchymal stem cell marker that is expressed by a small fraction of SF ex vivo. We have analyzed the location and relative proportion of CD271+ cells in synovial tissues from rheumatoid arthritis (RA), osteoarthritis (OA) and normal (N) individuals as well as their ex vivo functional properties in CD271+/- SF sorted cultures.

Methods

CD271 expression was analyzed by immunohistochemistry (IHC) in synovial tissues, and by flow cytometry (FC) in SF cultures from RA (n=10), OA (n=10), and normal synovial tissues (n=6). Isolation of CD271+ and CD271- OA SF (n=3) was carried out by magnetic beads sorting in passage 0 from OA explants. Supernatants of sorted CD271+/- SF were analyzed for IL-6, IL-8, MCP-1, MMP-1, MMP-3 and VEGF production by multiplex ELISA array (RayBiotech, Norcross, GA, USA). IL-6 data were confirmed by single specific ELISA. Quantitative data were analyzed by Mann-Whitney or ANOVA test where appropriate. 

Results

CD271+ cells were observed by IHC in all types of synovial tissues with a perivascular distribution partially resembling pericytes. The number of CD271+ cells per area was significantly increased in both RA and OA tissues compared to normal synovial tissues (772±206, 802±221 and 206±100 per mm2 respectively, p<0.0001 ANOVA). The frequency of CD271+ cells in SF cultures was highly variable but a trend towards a higher proportion of CD271+ cells in OA compared to RA and normal established SF cultures was observed (5.1±4.0%, 1.4±0.9% and 1.5±0.8% respectively). In individual OA SF cultures, cell passaging from passage 0 to 5 induced a progressive decrease in the percentage of CD271+ cells. OA CD271+ SF cultures sorted at passage 0 released significantly more IL-6 (3.1-fold increase) and metalloprotease MMP-1 (8.1-fold increase) than CD271- SF. A non-significant trend towards more IL-8, MMP-3 and VEGF production in CD271+ SF was also observed. MCP-1 production was similar in both SF subsets. 

Conclusion

Our results demonstrate an expansion of CD271+ perivascular cells in inflammatory RA and OA synovial tissues. Cultured CD271+ SF showed increased production of proinflammatory factors ex vivo compared to CD271- SF. These data suggest that CD271+ stromal cells could play a proinflammatory role in OA and RA synovium.

Disclosure:

M. J. Del Rey,
None;

R. Faré,
None;

G. Criado,
None;

A. Usategui,
None;

V. Miranda,
None;

J. D. Cañete,
None;

J. L. Pablos,
None.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/neurotrophin-receptor-p75-cd271-defines-a-distinct-synovial-fibroblast-subset-in-rheumatoid-and-osteoarthritic-synovial-tissues-with-enhanced-proinflammatory-potential/