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Crosstalk between FLS and chondrocytes is regulated by HIF-2α-mediated cytokines in arthritis

Rheumatoid arthritis (RA) and osteoarthritis (OA), two common types of arthritis, affect the joints mainly by targeting the synovium and cartilage. Increasing evidence indicates that a significant network connects synovitis and cartilage destruction during the progression of arthritis. We recently d...

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Autores principales: Huh, Yun Hyun, Lee, Gyuseok, Song, Won-Hyun, Koh, Jeong-Tae, Ryu, Je-Hwang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4686694/
https://www.ncbi.nlm.nih.gov/pubmed/26642431
http://dx.doi.org/10.1038/emm.2015.88
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author Huh, Yun Hyun
Lee, Gyuseok
Song, Won-Hyun
Koh, Jeong-Tae
Ryu, Je-Hwang
author_facet Huh, Yun Hyun
Lee, Gyuseok
Song, Won-Hyun
Koh, Jeong-Tae
Ryu, Je-Hwang
author_sort Huh, Yun Hyun
collection PubMed
description Rheumatoid arthritis (RA) and osteoarthritis (OA), two common types of arthritis, affect the joints mainly by targeting the synovium and cartilage. Increasing evidence indicates that a significant network connects synovitis and cartilage destruction during the progression of arthritis. We recently demonstrated that hypoxia-inducible factor (HIF)-2α causes RA and OA by regulating the expression of catabolic factors in fibroblast-like synoviocytes (FLS) or chondrocytes. To address the reciprocal influences of HIF-2α on FLS and chondrocytes, we applied an in vitro co-culture system using a transwell apparatus. When co-cultured with HIF-2α-overexpressing chondrocytes, FLS exhibited increased expression of matrix metalloproteinases and inflammatory mediators, similar to the effects induced by tumor-necrosis factor (TNF)-α treatment of FLS. Moreover, chondrocytes co-cultured with HIF-2α-overexpressing FLS exhibited upregulation of Mmp3 and Mmp13, which is similar to the effects induced by interleukin (IL)-6 treatment of chondrocytes. We confirmed these differential HIF-2α-induced effects via distinct secretory mediators using Il6-knockout cells and a TNF-α-blocking antibody. The FLS-co-culture-induced gene expression changes in chondrocytes were significantly abrogated by IL-6 deficiency, whereas TNF-α neutralization blocked the alterations in gene expression associated with co-culture of FLS with chondrocytes. Our results further suggested that the observed changes might reflect the HIF-2α-induced upregulation of specific receptors for TNF-α (in FLS) and IL-6 (in chondrocytes). This study broadens our understanding of the possible regulatory mechanisms underlying the crosstalk between the synovium and cartilage in the presence of HIF-2α, and may suggest potential new anti-arthritis therapies.
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spelling pubmed-46866942015-12-30 Crosstalk between FLS and chondrocytes is regulated by HIF-2α-mediated cytokines in arthritis Huh, Yun Hyun Lee, Gyuseok Song, Won-Hyun Koh, Jeong-Tae Ryu, Je-Hwang Exp Mol Med Original Article Rheumatoid arthritis (RA) and osteoarthritis (OA), two common types of arthritis, affect the joints mainly by targeting the synovium and cartilage. Increasing evidence indicates that a significant network connects synovitis and cartilage destruction during the progression of arthritis. We recently demonstrated that hypoxia-inducible factor (HIF)-2α causes RA and OA by regulating the expression of catabolic factors in fibroblast-like synoviocytes (FLS) or chondrocytes. To address the reciprocal influences of HIF-2α on FLS and chondrocytes, we applied an in vitro co-culture system using a transwell apparatus. When co-cultured with HIF-2α-overexpressing chondrocytes, FLS exhibited increased expression of matrix metalloproteinases and inflammatory mediators, similar to the effects induced by tumor-necrosis factor (TNF)-α treatment of FLS. Moreover, chondrocytes co-cultured with HIF-2α-overexpressing FLS exhibited upregulation of Mmp3 and Mmp13, which is similar to the effects induced by interleukin (IL)-6 treatment of chondrocytes. We confirmed these differential HIF-2α-induced effects via distinct secretory mediators using Il6-knockout cells and a TNF-α-blocking antibody. The FLS-co-culture-induced gene expression changes in chondrocytes were significantly abrogated by IL-6 deficiency, whereas TNF-α neutralization blocked the alterations in gene expression associated with co-culture of FLS with chondrocytes. Our results further suggested that the observed changes might reflect the HIF-2α-induced upregulation of specific receptors for TNF-α (in FLS) and IL-6 (in chondrocytes). This study broadens our understanding of the possible regulatory mechanisms underlying the crosstalk between the synovium and cartilage in the presence of HIF-2α, and may suggest potential new anti-arthritis therapies. Nature Publishing Group 2015-12 2015-12-04 /pmc/articles/PMC4686694/ /pubmed/26642431 http://dx.doi.org/10.1038/emm.2015.88 Text en Copyright © 2015 KSBMB. http://creativecommons.org/licenses/by-nc-nd/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/4.0/
spellingShingle Original Article
Huh, Yun Hyun
Lee, Gyuseok
Song, Won-Hyun
Koh, Jeong-Tae
Ryu, Je-Hwang
Crosstalk between FLS and chondrocytes is regulated by HIF-2α-mediated cytokines in arthritis
title Crosstalk between FLS and chondrocytes is regulated by HIF-2α-mediated cytokines in arthritis
title_full Crosstalk between FLS and chondrocytes is regulated by HIF-2α-mediated cytokines in arthritis
title_fullStr Crosstalk between FLS and chondrocytes is regulated by HIF-2α-mediated cytokines in arthritis
title_full_unstemmed Crosstalk between FLS and chondrocytes is regulated by HIF-2α-mediated cytokines in arthritis
title_short Crosstalk between FLS and chondrocytes is regulated by HIF-2α-mediated cytokines in arthritis
title_sort crosstalk between fls and chondrocytes is regulated by hif-2α-mediated cytokines in arthritis
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4686694/
https://www.ncbi.nlm.nih.gov/pubmed/26642431
http://dx.doi.org/10.1038/emm.2015.88
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