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

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...

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Autores principales: Deroyer, Céline, Charlier, Edith, Neuville, Sophie, Malaise, Olivier, Gillet, Philippe, Kurth, William, Chariot, Alain, Malaise, Michel, de Seny, Dominique
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6362103/
https://www.ncbi.nlm.nih.gov/pubmed/30718510
http://dx.doi.org/10.1038/s41419-019-1377-8
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author Deroyer, Céline
Charlier, Edith
Neuville, Sophie
Malaise, Olivier
Gillet, Philippe
Kurth, William
Chariot, Alain
Malaise, Michel
de Seny, Dominique
author_facet Deroyer, Céline
Charlier, Edith
Neuville, Sophie
Malaise, Olivier
Gillet, Philippe
Kurth, William
Chariot, Alain
Malaise, Michel
de Seny, Dominique
author_sort Deroyer, Céline
collection PubMed
description 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.
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spelling pubmed-63621032019-02-05 CEMIP (KIAA1199) induces a fibrosis-like process in osteoarthritic chondrocytes Deroyer, Céline Charlier, Edith Neuville, Sophie Malaise, Olivier Gillet, Philippe Kurth, William Chariot, Alain Malaise, Michel de Seny, Dominique Cell Death Dis Article 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. Nature Publishing Group UK 2019-02-04 /pmc/articles/PMC6362103/ /pubmed/30718510 http://dx.doi.org/10.1038/s41419-019-1377-8 Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Deroyer, Céline
Charlier, Edith
Neuville, Sophie
Malaise, Olivier
Gillet, Philippe
Kurth, William
Chariot, Alain
Malaise, Michel
de Seny, Dominique
CEMIP (KIAA1199) induces a fibrosis-like process in osteoarthritic chondrocytes
title CEMIP (KIAA1199) induces a fibrosis-like process in osteoarthritic chondrocytes
title_full CEMIP (KIAA1199) induces a fibrosis-like process in osteoarthritic chondrocytes
title_fullStr CEMIP (KIAA1199) induces a fibrosis-like process in osteoarthritic chondrocytes
title_full_unstemmed CEMIP (KIAA1199) induces a fibrosis-like process in osteoarthritic chondrocytes
title_short CEMIP (KIAA1199) induces a fibrosis-like process in osteoarthritic chondrocytes
title_sort cemip (kiaa1199) induces a fibrosis-like process in osteoarthritic chondrocytes
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6362103/
https://www.ncbi.nlm.nih.gov/pubmed/30718510
http://dx.doi.org/10.1038/s41419-019-1377-8
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