CEMIP (KIAA1199) induces a fibrosis-like process in osteoarthritic 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.

Disciplines :

Rheumatology

Author, co-author :

DEROYER, Céline ; Centre Hospitalier Universitaire de Liège - CHU > Département de médecine interne > Service de rhumatologie

CHARLIER, Edith ; Centre Hospitalier Universitaire de Liège - CHU > Département de médecine interne > Service de rhumatologie

NEUVILLE, Sophie ; Centre Hospitalier Universitaire de Liège - CHU > Département de médecine interne > Service de rhumatologie

MALAISE, Olivier ; Centre Hospitalier Universitaire de Liège - CHU > Département de médecine interne > Service de rhumatologie

GILLET, Philippe ; Centre Hospitalier Universitaire de Liège - CHU > Département de chirurgie > Service de chirurgie de l'appareil locomoteur

KURTH, William ; Centre Hospitalier Universitaire de Liège - CHU > Département de chirurgie > Service de chirurgie de l'appareil locomoteur

Chariot, Alain ; Université de Liège - ULiège > Département de pharmacie > Chimie médicale

MALAISE, Michel ; Centre Hospitalier Universitaire de Liège - CHU > Département de médecine interne > Service de rhumatologie

DE SENY, Dominique ; Centre Hospitalier Universitaire de Liège - CHU > Département de médecine interne > Service de rhumatologie

Language :

English

Title :

CEMIP (KIAA1199) induces a fibrosis-like process in osteoarthritic chondrocytes

Publication date :

04 February 2019

Journal title :

Cell Death and Disease

eISSN :

2041-4889

Publisher :

Nature Publishing Group, United Kingdom

Peer reviewed :

Peer Reviewed verified by ORBi

Available on ORBi :

since 08 February 2019

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