A Human Osteochondral Tissue Model Mimicking Cytokine-Induced Key Features of Arthritis In Vitro

A Human Osteochondral Tissue Model Mimicking Cytokine-Induced Key Features of Arthritis In Vitro

Adequate tissue engineered models are required to further understand the (patho)physiological mechanism involved in the destructive processes of cartilage and subchondral bone during rheumatoid arthritis (RA). Therefore, we developed a human in vitro 3D osteochondral tissue model (OTM), mimicking cy...

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Main Authors: Alexandra Damerau, Moritz Pfeiffenberger, Marie-Christin Weber, Gerd-Rüdiger Burmester, Frank Buttgereit, Timo Gaber, Annemarie Lang
Format: Article
Language:English
Published: MDPI AG 2021-12-01
Series:International Journal of Molecular Sciences
Subjects:
mesenchymal stem cells
tissue engineering
osteochondral unit
in vitro model
rheumatoid arthritis
Online Access:https://www.mdpi.com/1422-0067/22/1/128
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spelling doaj-7f3220e92fb248feb514f8bc24a591bc2020-12-25T00:05:40ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-12-012212812810.3390/ijms22010128A Human Osteochondral Tissue Model Mimicking Cytokine-Induced Key Features of Arthritis In VitroAlexandra Damerau0Moritz Pfeiffenberger1Marie-Christin Weber2Gerd-Rüdiger Burmester3Frank Buttgereit4Timo Gaber5Annemarie Lang6Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Rheumatology and Clinical Immunology, 10117 Berlin, GermanyCharité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Rheumatology and Clinical Immunology, 10117 Berlin, GermanyCharité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Rheumatology and Clinical Immunology, 10117 Berlin, GermanyCharité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Rheumatology and Clinical Immunology, 10117 Berlin, GermanyCharité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Rheumatology and Clinical Immunology, 10117 Berlin, GermanyCharité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Rheumatology and Clinical Immunology, 10117 Berlin, GermanyCharité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Rheumatology and Clinical Immunology, 10117 Berlin, GermanyAdequate tissue engineered models are required to further understand the (patho)physiological mechanism involved in the destructive processes of cartilage and subchondral bone during rheumatoid arthritis (RA). Therefore, we developed a human in vitro 3D osteochondral tissue model (OTM), mimicking cytokine-induced cellular and matrix-related changes leading to cartilage degradation and bone destruction in order to ultimately provide a preclinical drug screening tool. To this end, the OTM was engineered by co-cultivation of mesenchymal stromal cell (MSC)-derived bone and cartilage components in a 3D environment. It was comprehensively characterized on cell, protein, and mRNA level. Stimulating the OTM with proinflammatory cytokines, relevant in RA (tumor necrosis factor α, interleukin-6, macrophage migration inhibitory factor ), caused cell- and matrix-related changes, resulting in a significantly induced the gene expression of lactate dehydrogenase A, interleukin-8 and tumor necrosis factor αin both, cartilage, and bone, while the matrix metalloproteases (MMPs) <i>MMP1</i> and <i>MMP3</i> expression were only induced in cartilage. Finally, application of target-specific drugs prevented the induction of inflammation and matrix-degradation. Thus, we here provide evidence that our human in vitro 3D OTM mimics cytokine-induced cell- and matrix-related changes—key features of RA—and may serve as a preclinical tool for the evaluation of both new targets and potential drugs in a more translational setup.https://www.mdpi.com/1422-0067/22/1/128mesenchymal stem cellstissue engineeringosteochondral unitin vitro modelrheumatoid arthritis
collection DOAJ
language English
format Article
sources DOAJ
author Alexandra Damerau
Moritz Pfeiffenberger
Marie-Christin Weber
Gerd-Rüdiger Burmester
Frank Buttgereit
Timo Gaber
Annemarie Lang
spellingShingle Alexandra Damerau
Moritz Pfeiffenberger
Marie-Christin Weber
Gerd-Rüdiger Burmester
Frank Buttgereit
Timo Gaber
Annemarie Lang
A Human Osteochondral Tissue Model Mimicking Cytokine-Induced Key Features of Arthritis In Vitro
International Journal of Molecular Sciences
mesenchymal stem cells
tissue engineering
osteochondral unit
in vitro model
rheumatoid arthritis
author_facet Alexandra Damerau
Moritz Pfeiffenberger
Marie-Christin Weber
Gerd-Rüdiger Burmester
Frank Buttgereit
Timo Gaber
Annemarie Lang
author_sort Alexandra Damerau
title A Human Osteochondral Tissue Model Mimicking Cytokine-Induced Key Features of Arthritis In Vitro
title_short A Human Osteochondral Tissue Model Mimicking Cytokine-Induced Key Features of Arthritis In Vitro
title_full A Human Osteochondral Tissue Model Mimicking Cytokine-Induced Key Features of Arthritis In Vitro
title_fullStr A Human Osteochondral Tissue Model Mimicking Cytokine-Induced Key Features of Arthritis In Vitro
title_full_unstemmed A Human Osteochondral Tissue Model Mimicking Cytokine-Induced Key Features of Arthritis In Vitro
title_sort human osteochondral tissue model mimicking cytokine-induced key features of arthritis in vitro
publisher MDPI AG
series International Journal of Molecular Sciences
issn 1661-6596
1422-0067
publishDate 2021-12-01
description Adequate tissue engineered models are required to further understand the (patho)physiological mechanism involved in the destructive processes of cartilage and subchondral bone during rheumatoid arthritis (RA). Therefore, we developed a human in vitro 3D osteochondral tissue model (OTM), mimicking cytokine-induced cellular and matrix-related changes leading to cartilage degradation and bone destruction in order to ultimately provide a preclinical drug screening tool. To this end, the OTM was engineered by co-cultivation of mesenchymal stromal cell (MSC)-derived bone and cartilage components in a 3D environment. It was comprehensively characterized on cell, protein, and mRNA level. Stimulating the OTM with proinflammatory cytokines, relevant in RA (tumor necrosis factor α, interleukin-6, macrophage migration inhibitory factor ), caused cell- and matrix-related changes, resulting in a significantly induced the gene expression of lactate dehydrogenase A, interleukin-8 and tumor necrosis factor αin both, cartilage, and bone, while the matrix metalloproteases (MMPs) <i>MMP1</i> and <i>MMP3</i> expression were only induced in cartilage. Finally, application of target-specific drugs prevented the induction of inflammation and matrix-degradation. Thus, we here provide evidence that our human in vitro 3D OTM mimics cytokine-induced cell- and matrix-related changes—key features of RA—and may serve as a preclinical tool for the evaluation of both new targets and potential drugs in a more translational setup.
topic mesenchymal stem cells
tissue engineering
osteochondral unit
in vitro model
rheumatoid arthritis
url https://www.mdpi.com/1422-0067/22/1/128
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