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: Fibroblasts, Mesenchymal stem cells, Osteoarthritis, rheumatoid arthritis (RA) and synovial cells, synovial fluid

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/