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Establishment of an Ex Vivo Inflammatory Osteoarthritis Model With Human Osteochondral Explants

Osteoarthritis (OA) is the most common degenerative joint disease without clear pathophysiological mechanism and effective drugs for treatment. Although various animal models exist, the translation of the outcome into clinics remains difficult due to species differences. In this study, an ex vivo in...

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Autores principales: Li, Kaihu, Zhang, Penghui, Zhu, Yong, Alini, Mauro, Grad, Sibylle, Li, Zhen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8724558/
https://www.ncbi.nlm.nih.gov/pubmed/34993189
http://dx.doi.org/10.3389/fbioe.2021.787020
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author Li, Kaihu
Zhang, Penghui
Zhu, Yong
Alini, Mauro
Grad, Sibylle
Li, Zhen
author_facet Li, Kaihu
Zhang, Penghui
Zhu, Yong
Alini, Mauro
Grad, Sibylle
Li, Zhen
author_sort Li, Kaihu
collection PubMed
description Osteoarthritis (OA) is the most common degenerative joint disease without clear pathophysiological mechanism and effective drugs for treatment. Although various animal models exist, the translation of the outcome into clinics remains difficult due to species differences. In this study, an ex vivo inflammatory OA model was induced using different concentrations of interleukin one beta (IL-1β) and tumor necrosis factor α (TNF-α) on explants from the human femoral head. In the inflammatory OA groups, the gene expression levels of cartilage catabolism (matrix metalloproteinase 1 (MMP1), matrix metalloproteinase 3 (MMP3)), and inflammation (interleukin 6 (IL-6), interleukin 8 (IL-8)) markers were significantly upregulated, while the anabolic genes (collagen 2 (COL2), aggrecan (ACAN), and proteoglycan 4 (PRG4)) were downregulated compared to the control group. The release of cytokines (IL-6, IL-8) and nitric oxide (NO) in the conditioned medium was also upregulated in inflammatory OA groups. The Safranin O/Fast Green staining showed loss of proteoglycan in the superficial zone cartilage after cytokine treatment. The results indicated that an ex vivo inflammation and degeneration model was successfully established using osteochondral explants from the human femoral head. This model can be used to elucidate the in-depth mechanism of inflammatory OA and to screen new drugs for OA treatment.
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spelling pubmed-87245582022-01-05 Establishment of an Ex Vivo Inflammatory Osteoarthritis Model With Human Osteochondral Explants Li, Kaihu Zhang, Penghui Zhu, Yong Alini, Mauro Grad, Sibylle Li, Zhen Front Bioeng Biotechnol Bioengineering and Biotechnology Osteoarthritis (OA) is the most common degenerative joint disease without clear pathophysiological mechanism and effective drugs for treatment. Although various animal models exist, the translation of the outcome into clinics remains difficult due to species differences. In this study, an ex vivo inflammatory OA model was induced using different concentrations of interleukin one beta (IL-1β) and tumor necrosis factor α (TNF-α) on explants from the human femoral head. In the inflammatory OA groups, the gene expression levels of cartilage catabolism (matrix metalloproteinase 1 (MMP1), matrix metalloproteinase 3 (MMP3)), and inflammation (interleukin 6 (IL-6), interleukin 8 (IL-8)) markers were significantly upregulated, while the anabolic genes (collagen 2 (COL2), aggrecan (ACAN), and proteoglycan 4 (PRG4)) were downregulated compared to the control group. The release of cytokines (IL-6, IL-8) and nitric oxide (NO) in the conditioned medium was also upregulated in inflammatory OA groups. The Safranin O/Fast Green staining showed loss of proteoglycan in the superficial zone cartilage after cytokine treatment. The results indicated that an ex vivo inflammation and degeneration model was successfully established using osteochondral explants from the human femoral head. This model can be used to elucidate the in-depth mechanism of inflammatory OA and to screen new drugs for OA treatment. Frontiers Media S.A. 2021-12-21 /pmc/articles/PMC8724558/ /pubmed/34993189 http://dx.doi.org/10.3389/fbioe.2021.787020 Text en Copyright © 2021 Li, Zhang, Zhu, Alini, Grad and Li. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Bioengineering and Biotechnology
Li, Kaihu
Zhang, Penghui
Zhu, Yong
Alini, Mauro
Grad, Sibylle
Li, Zhen
Establishment of an Ex Vivo Inflammatory Osteoarthritis Model With Human Osteochondral Explants
title Establishment of an Ex Vivo Inflammatory Osteoarthritis Model With Human Osteochondral Explants
title_full Establishment of an Ex Vivo Inflammatory Osteoarthritis Model With Human Osteochondral Explants
title_fullStr Establishment of an Ex Vivo Inflammatory Osteoarthritis Model With Human Osteochondral Explants
title_full_unstemmed Establishment of an Ex Vivo Inflammatory Osteoarthritis Model With Human Osteochondral Explants
title_short Establishment of an Ex Vivo Inflammatory Osteoarthritis Model With Human Osteochondral Explants
title_sort establishment of an ex vivo inflammatory osteoarthritis model with human osteochondral explants
topic Bioengineering and Biotechnology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8724558/
https://www.ncbi.nlm.nih.gov/pubmed/34993189
http://dx.doi.org/10.3389/fbioe.2021.787020
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