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Identifier

000463643

Title

Characterization of Synovial Fibroblasts

Alternative Title

Χαρακτηρισμός των Ινοβλαστών του Αρθρικού Υμένα

Author

Τοϊτου, Μελπομένη

Thesis advisor

Σιδηρόπουλος, Πρόδρομος
Μπερτσιάς, Γεώργιος
Βεργίνης, Παναγιώτης
Ospelt, Caroline

Abstract

In our study, we aimed to comprehensively characterize the topographical organization and functional properties of synovial fibroblast (SF) subtypes in rheumatoid arthritis (RA) and osteoarthritis (OA) patients. Using immunohistochemistry (IHC), we investigated the spatial distribution of SF subtypes within the synovium, revealing distinct localization patterns for each subtype. PRG4+ SFs were predominantly found in the lining layer and cartilage-invading regions, implicating their role in joint destruction. POSTN+ SFs exhibited a perivascular distribution, while MFAP5+ SFs expanded throughout the sublining layer. CXCL12+ CD74+ SFs were enriched in inflammatory areas, particularly near SPP1-expressing macrophages. Furthermore, we conducted functional assays on isolated SF subtypes to elucidate their roles in inflammation, matrix remodeling, and immune modulation. CXCL12+CD74+ SFs demonstrated immune-effector functions, promoting IL-6 secretion and activating macrophages. Surprisingly, both CXCL12+CD74+ and CD90- SFs tended to induce osteoclast differentiation, potentially contributing to joint damage. Additionally, we investigated the impact of SF subtypes on angiogenesis, revealing a decreased capacity across all subtypes compared to healthy SFs. Our findings suggested a complex interplay between SF subtypes, immune cells, and the microenvironment in Arthritis pathogenesis. We further investigated the immune-effector CXCL12+CD74+ SFs. More specifically, we assessed the acquisition of the CD74+ phenotype in cultured SFs following co-culture with RA T-cells.To recapitulate the synovial microenvironment, we incorporated SFs that acquired CD74 expression into a 3D synovial and revealed altered interactions with macrophages. In conclusion, our study provides novel insights into the heterogeneity and functional diversity of SF subtypes, highlighting their potential contributions to joint inflammation, destruction, and immune dysregulation. These findings offer promising avenues for targeted therapeutic interventions aimed at modulating specific SF subpopulations to mitigate disease progression in Arthritis.

Language

English

Subject

Arthritis

Synovium

Αρθρίτιδα

Ινιβλάστες

Υμένας

Issue date

2024-04-17

Collection

School/Department--School of Medicine--Department of Medicine--Post-graduate theses