Reference : CEMIP (KIAA1199) induces a fibrosis-like process in osteoarthritic chondrocytes
Scientific journals : Article
Human health sciences : Rheumatology
http://hdl.handle.net/2268/232764
CEMIP (KIAA1199) induces a fibrosis-like process in osteoarthritic chondrocytes
English
DEROYER, Céline mailto [Centre Hospitalier Universitaire de Liège - CHU > Département de médecine interne > Service de rhumatologie >]
CHARLIER, Edith mailto [Centre Hospitalier Universitaire de Liège - CHU > Département de médecine interne > Service de rhumatologie >]
NEUVILLE, Sophie mailto [Centre Hospitalier Universitaire de Liège - CHU > Département de médecine interne > Service de rhumatologie >]
MALAISE, Olivier mailto [Centre Hospitalier Universitaire de Liège - CHU > Département de médecine interne > Service de rhumatologie >]
GILLET, Philippe mailto [Centre Hospitalier Universitaire de Liège - CHU > Département de chirurgie > Service de chirurgie de l'appareil locomoteur >]
KURTH, William mailto [Centre Hospitalier Universitaire de Liège - CHU > Département de chirurgie > Service de chirurgie de l'appareil locomoteur >]
Chariot, Alain mailto [Université de Liège - ULiège > Département de pharmacie > Chimie médicale >]
MALAISE, Michel mailto [Centre Hospitalier Universitaire de Liège - CHU > Département de médecine interne > Service de rhumatologie >]
DE SENY, Dominique mailto [Centre Hospitalier Universitaire de Liège - CHU > Département de médecine interne > Service de rhumatologie >]
4-Feb-2019
Cell Death and Disease
Nature Publishing Group
Yes (verified by ORBi)
International
2041-4889
United Kingdom
[en] Osteoarthritis ; Fibrosis ; Chondrocytes
[en] CEMIP (for “Cell migration-inducing protein” also called KIAA1199 and Hybid for “Hyaluronan-binding protein”) expression is increased in cancers and described as a regulator of cell survival, growth and invasion. In rheumatoid arthritis, CEMIP is referred to as an angiogenic marker and participates in hyaluronic acid degradation. In this study, CEMIP expression is investigated in healthy and osteoarthritis (OA) cartilage from human and mouse. Its role in OA physiopathology is deciphered, specifically in chondrocytes proliferation and dedifferentiation and in the extracellular matrix remodeling. To this end, CEMIP, αSMA and types I and III collagen expressions were assessed in human OA and non-OA cartilage. CEMIP expression was also investigated in a mouse OA model. CEMIP expression was studied in vitro using a chondrocyte dedifferentiation model. High-throughput RNA sequencing was performed on chondrocytes after CEMIP silencing. Results showed that CEMIP was overexpressed in human and murine OA cartilage and along chondrocytes dedifferentiation. Most of genes deregulated in CEMIP-depleted cells were involved in cartilage turnover (e.g., collagens), mesenchymal transition and fibrosis. CEMIP regulated β-catenin protein level. Moreover, CEMIP was essential for chondrocytes proliferation and promoted αSMA expression, a fibrosis marker, and TGFβ signaling towards the p-Smad2/3 (Alk5/PAI-1) pathway. Interestingly, CEMIP was induced by the pSmad1/5 (Alk1) pathway. αSMA and type III collagen expressions were overexpressed in human OA cartilage and along chondrocytes dedifferentiation. Finally, CEMIP was co-expressed in situ with αSMA in all OA cartilage layers. In conclusion, CEMIP was sharply overexpressed in human and mouse OA cartilage and along chondrocytes dedifferentiation. CEMIP-regulated transdifferentiation of chondrocytes into “chondro-myo-fibroblasts” expressing α-SMA and type III collagen, two fibrosis markers. Moreover, these “chondro-myo-fibroblasts” were found in OA cartilage but not in healthy cartilage.
http://hdl.handle.net/2268/232764
10.1038/s41419-019-1377-8

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