Cargando…
Degrading products of chondroitin sulfate can induce hypertrophy-like changes and MMP-13/ADAMTS5 production in chondrocytes
Chondroitin sulfate (CS) is the most abundant glycosaminoglycan (GAG) in articular cartilage and the loss of CS-GAG occurs early in OA. As a major component of perichondral matrix interacting directly with chondrocytes, the active turnover of CS can affect to break the homeostasis of chondrocytes. H...
Autores principales: | , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2019
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6825126/ https://www.ncbi.nlm.nih.gov/pubmed/31676809 http://dx.doi.org/10.1038/s41598-019-52358-4 |
_version_ | 1783464841544990720 |
---|---|
author | Jung, Youn-Kwan Park, Hye-Ri Cho, Hyun-Jung Jang, Ji-Ae Lee, Eun-Ju Han, Min-Su Kim, Gun-Woo Han, Seungwoo |
author_facet | Jung, Youn-Kwan Park, Hye-Ri Cho, Hyun-Jung Jang, Ji-Ae Lee, Eun-Ju Han, Min-Su Kim, Gun-Woo Han, Seungwoo |
author_sort | Jung, Youn-Kwan |
collection | PubMed |
description | Chondroitin sulfate (CS) is the most abundant glycosaminoglycan (GAG) in articular cartilage and the loss of CS-GAG occurs early in OA. As a major component of perichondral matrix interacting directly with chondrocytes, the active turnover of CS can affect to break the homeostasis of chondrocytes. Here we employ CS-based 3-dimensional (3D) hydrogel scaffold system to investigate how the degradation products of CS affect the catabolic phenotype of chondrocytes. The breakdown of CS-based ECM by the chondroitinase ABC (ChABC) resulted in a hypertrophy-like morphologic change in chondrocytes, which was accompanied by catabolic phenotypes, including increased MMP-13 and ADAMTS5 expression, nitric oxide (NO) production and oxidative stress. The inhibition of Toll-like receptor 2 (TLR2) or TLR4 with OxPAPC (TLR2 and TLR4 dual inhibitor) and LPS-RS (TLR4-MD2 inhibitor) ameliorated these catabolic phenotypes of chondrocytes by CS-ECM degradation, suggesting a role of CS breakdown products as damage-associated molecular patterns (DAMPs). As downstream signals of TLRs, MAP kinases, NF-kB, NO and STAT3-related signals were responsible for the catabolic phenotypes of chondrocytes associated with ECM degradation. NO in turn reinforced the activation of MAP kinases as well as NFkB signaling pathway. Thus, these results propose that the breakdown product of CS-GAG can recapitulate the catabolic phenotypes of OA. |
format | Online Article Text |
id | pubmed-6825126 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-68251262019-11-12 Degrading products of chondroitin sulfate can induce hypertrophy-like changes and MMP-13/ADAMTS5 production in chondrocytes Jung, Youn-Kwan Park, Hye-Ri Cho, Hyun-Jung Jang, Ji-Ae Lee, Eun-Ju Han, Min-Su Kim, Gun-Woo Han, Seungwoo Sci Rep Article Chondroitin sulfate (CS) is the most abundant glycosaminoglycan (GAG) in articular cartilage and the loss of CS-GAG occurs early in OA. As a major component of perichondral matrix interacting directly with chondrocytes, the active turnover of CS can affect to break the homeostasis of chondrocytes. Here we employ CS-based 3-dimensional (3D) hydrogel scaffold system to investigate how the degradation products of CS affect the catabolic phenotype of chondrocytes. The breakdown of CS-based ECM by the chondroitinase ABC (ChABC) resulted in a hypertrophy-like morphologic change in chondrocytes, which was accompanied by catabolic phenotypes, including increased MMP-13 and ADAMTS5 expression, nitric oxide (NO) production and oxidative stress. The inhibition of Toll-like receptor 2 (TLR2) or TLR4 with OxPAPC (TLR2 and TLR4 dual inhibitor) and LPS-RS (TLR4-MD2 inhibitor) ameliorated these catabolic phenotypes of chondrocytes by CS-ECM degradation, suggesting a role of CS breakdown products as damage-associated molecular patterns (DAMPs). As downstream signals of TLRs, MAP kinases, NF-kB, NO and STAT3-related signals were responsible for the catabolic phenotypes of chondrocytes associated with ECM degradation. NO in turn reinforced the activation of MAP kinases as well as NFkB signaling pathway. Thus, these results propose that the breakdown product of CS-GAG can recapitulate the catabolic phenotypes of OA. Nature Publishing Group UK 2019-11-01 /pmc/articles/PMC6825126/ /pubmed/31676809 http://dx.doi.org/10.1038/s41598-019-52358-4 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 Jung, Youn-Kwan Park, Hye-Ri Cho, Hyun-Jung Jang, Ji-Ae Lee, Eun-Ju Han, Min-Su Kim, Gun-Woo Han, Seungwoo Degrading products of chondroitin sulfate can induce hypertrophy-like changes and MMP-13/ADAMTS5 production in chondrocytes |
title | Degrading products of chondroitin sulfate can induce hypertrophy-like changes and MMP-13/ADAMTS5 production in chondrocytes |
title_full | Degrading products of chondroitin sulfate can induce hypertrophy-like changes and MMP-13/ADAMTS5 production in chondrocytes |
title_fullStr | Degrading products of chondroitin sulfate can induce hypertrophy-like changes and MMP-13/ADAMTS5 production in chondrocytes |
title_full_unstemmed | Degrading products of chondroitin sulfate can induce hypertrophy-like changes and MMP-13/ADAMTS5 production in chondrocytes |
title_short | Degrading products of chondroitin sulfate can induce hypertrophy-like changes and MMP-13/ADAMTS5 production in chondrocytes |
title_sort | degrading products of chondroitin sulfate can induce hypertrophy-like changes and mmp-13/adamts5 production in chondrocytes |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6825126/ https://www.ncbi.nlm.nih.gov/pubmed/31676809 http://dx.doi.org/10.1038/s41598-019-52358-4 |
work_keys_str_mv | AT jungyounkwan degradingproductsofchondroitinsulfatecaninducehypertrophylikechangesandmmp13adamts5productioninchondrocytes AT parkhyeri degradingproductsofchondroitinsulfatecaninducehypertrophylikechangesandmmp13adamts5productioninchondrocytes AT chohyunjung degradingproductsofchondroitinsulfatecaninducehypertrophylikechangesandmmp13adamts5productioninchondrocytes AT jangjiae degradingproductsofchondroitinsulfatecaninducehypertrophylikechangesandmmp13adamts5productioninchondrocytes AT leeeunju degradingproductsofchondroitinsulfatecaninducehypertrophylikechangesandmmp13adamts5productioninchondrocytes AT hanminsu degradingproductsofchondroitinsulfatecaninducehypertrophylikechangesandmmp13adamts5productioninchondrocytes AT kimgunwoo degradingproductsofchondroitinsulfatecaninducehypertrophylikechangesandmmp13adamts5productioninchondrocytes AT hanseungwoo degradingproductsofchondroitinsulfatecaninducehypertrophylikechangesandmmp13adamts5productioninchondrocytes |