Le mercredi 1er juillet 2026, Madame Zoé GENDEBIEN, titulaire d'un d’un Master en médecine et d’un Certificat de formation à la recherche en sciences médicales, présentera l'examen en vue de l'obtention du grade de Doctorat en sciences médicales, sous la direction de Madame Clio RIBBENS et de Madame Dominique DE SENY.

Cette épreuve consistera en la défense publique d'une thèse intitulée : "Role of endoplasmic reticulum stress proteins in the pathogenesis of synovitis in osteoarthritis". 

Le jury sera composé de :

François JOURET (Président), Thomas MARICHAL (Secrétaire), Dominique DE SENY, Nisha LIMAYE (UCLouvain), Edouard LOUIS, Clio ROBBENS, Jérémie SELLAM (Hôp. St-Antoine)

Résumé de la thèse

Osteoarthritis (OA) is a highly prevalent joint disease and a major cause of pain. Initially considered as a degenerative cartilage disorder, OA is now recognized as a whole-joint disease, also involving the subchondral bone and the synovial membrane, where inflammatory and fibrotic processes contribute to the disease. 

A strong link exists between endoplasmic reticulum (ER) stress and synovitis. This thesis investigates the spatial distribution of ER chaperones and their functional contribution to synovitis in OA.

By immunohistochemistry, chaperones localized to the lining layer in non-inflamed OA synovium and progressively extended into the sublining with increasing inflammation. Imaging mass cytometry showed that chaperone expression was restricted to fibroblast-like synoviocytes (FLS), shifting from CD55⁺ lining fibroblasts in non-inflamed OA to CD34⁺ sublining fibroblasts in inflamed synovium, with no expression detected in lymphocytes. This spatial pattern was confirmed by immunofluorescence in a larger OA cohort. 

In vitro, ER stress proteins were overexpressed in human OA FLS following ER stress, pro-inflammatory, and/or pro-fibrotic stimulation. Among them, PDIA4 depletion significantly impaired fibroblast proliferation, a key hallmark of synovitis. This work provides the first spatial and functional characterization of ER chaperones in human arthritic synovium, linking ER stress to fibroblast plasticity, inflammation, and fibrosis.