CEMIP (KIAA1199) regulates inflammation, hyperplasia and fibrosis in osteoarthritis synovial membrane

• Published in: Cellular and molecular life sciences : CMLS Vol. 79; no. 5; p. 260
• Main Authors: Deroyer, Céline, Poulet, Christophe, Paulissen, Geneviève, Ciregia, Federica, Malaise, Olivier, Plener, Zelda, Cobraiville, Gaël, Daniel, Christophe, Gillet, Philippe, Malaise, Michel G., de Seny, Dominique
• Format: Journal Article Web Resource
• Language: English
• Published: Cham Springer International Publishing 01.05.2022; Springer Nature B.V; Birkhauser Verlag
• Subjects: Animals; Arthritis; Biochemistry; Biochemistry, biophysics & molecular biology; Biochimie, biophysique & biologie moléculaire; Biomedical and Life Sciences; Biomedical materials; Biomedicine; Cartilage; Cartilage diseases; Cell Biology; Cell growth; Cell proliferation; CEMIP, KIAA1199, Hybid, fibrosis, inflammation, osteoarthritis, synovitis; Collagen; Collagenase; Cytokines; Cytokines - metabolism; Epithelial-Mesenchymal Transition; Fibrosis; Humans; Hyaluronoglucosaminidase - metabolism; Hyperplasia; Hyperplasia - metabolism; Inflammation; Inflammation - pathology; Inflammatory response; Life Sciences; Membranes; Mesenchyme; Mice; Original; Original Article; Osteoarthritis; Osteoarthritis - metabolism; Sciences du vivant; Synovial membrane; Synovial Membrane - metabolism; Synovial Membrane - pathology; Synoviocytes; Synovitis; CEMIP; Hybid; Fibrosis; Inflammation; KIAA1199; Osteoarthritis
• ISSN: 1420-682X; 1420-9071; 1420-9071
• DOI: 10.1007/s00018-022-04282-6

Osteoarthritis (OA) synovial membrane is mainly characterized by low-grade inflammation, hyperplasia with increased cell proliferation and fibrosis. We previously underscored a critical role for CEMIP in fibrosis of OA cartilage. However, its role in OA synovial membrane remains unknown. An in vitro model with fibroblast-like synoviocytes from OA patients and an in vivo model with collagenase-induced OA mice were used to evaluate CEMIP-silencing effects on inflammation, hyperplasia and fibrosis. Our results showed that i. CEMIP expression was increased in human and mouse inflamed synovial membrane; ii. CEMIP regulated the inflammatory response pathway and inflammatory cytokines production in vitro and in vivo; iii. CEMIP induced epithelial to mesenchymal transition pathway and fibrotic markers in vitro and in vivo ; iv. CEMIP increased cell proliferation and synovial hyperplasia; v. CEMIP expression was increased by inflammatory cytokines and by TGF-β signaling; vi. anti-fibrotic drugs decreased CEMIP expression. All these findings highlighted the central role of CEMIP in OA synovial membrane development and underscored that targeting CEMIP could be a new therapeutic approach.