Comparison of Concentration- and Homology-Dependent Effects of the Proinflammatory Cytokine Interleukin-1β (IL-1β) in a Bovine Chondrocyte Inflammation Model

Inflammation models with the proinflammatory cytokine interleukin-1β (IL-1β) are widely used in the in vitro investigation of new therapeutic approaches for osteoarthritis (OA). The aim of this study was to systematically analyze the influence of IL-1β in a 3D chondral pellet culture model. Bovine a...

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Main Authors: Robert Ossendorff, Sarah Kurth, Su Wang, Max Jaenisch, Elio Assaf, Sebastian Scheidt, Kristian Welle, Christof Burger, Dieter C. Wirtz, Andreas C. Strauss, Frank A. Schildberg
Format: Article
Language:English
Published: MDPI AG 2024-12-01
Series:Cells
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Online Access:https://www.mdpi.com/2073-4409/14/1/30
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author Robert Ossendorff
Sarah Kurth
Su Wang
Max Jaenisch
Elio Assaf
Sebastian Scheidt
Kristian Welle
Christof Burger
Dieter C. Wirtz
Andreas C. Strauss
Frank A. Schildberg
author_facet Robert Ossendorff
Sarah Kurth
Su Wang
Max Jaenisch
Elio Assaf
Sebastian Scheidt
Kristian Welle
Christof Burger
Dieter C. Wirtz
Andreas C. Strauss
Frank A. Schildberg
author_sort Robert Ossendorff
collection DOAJ
description Inflammation models with the proinflammatory cytokine interleukin-1β (IL-1β) are widely used in the in vitro investigation of new therapeutic approaches for osteoarthritis (OA). The aim of this study was to systematically analyze the influence of IL-1β in a 3D chondral pellet culture model. Bovine articular chondrocytes were cultured to passage 3 and then placed in pellet culture. Titration of IL-1β (100–0.1 ng/mL) was performed with both human and bovine recombinant protein in chondrocyte culture for 2 weeks. Gene expression of anabolic (collagen 2, aggrecan, cartilage oligomeric protein (COMP), proteoglycan-4 (PRG-4)), catabolic matrix metallo proteinases (MMP-3, MMP-13), dedifferentiation (collagen 1) markers and inflammatory cytokines IL-6 and IL-8 was determined. Analysis of the cell culture medium was performed for the inflammatory markers IL-6 and nitric oxide (NO). In general, the influence of IL-1β was shown by a decrease in the expression of anabolic markers (collagen 2, aggrecan, PRG-4), whereas the catabolic markers MMP-3 and MMP-13 as well as the inflammatory markers IL-6 and IL-8 were significantly increased. This was observed both at the early time point (day 4) and at the late time point (day 14). The described inflammatory effects were confirmed by increased concentration-dependent release of NO and IL-6. The threshold concentration for a detectable effect compared to control differed between groups, but was reached earlier by homologous application of IL-1β. This study provides a systematic evaluation of IL-1β-specific effects on chondrocytes in a 3D pellet culture model, which is highly relevant for comparisons of studies in OA-specific drug development.
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spelling doaj-art-501388c887e349fea3bbb0626aca78412025-01-10T13:16:18ZengMDPI AGCells2073-44092024-12-011413010.3390/cells14010030Comparison of Concentration- and Homology-Dependent Effects of the Proinflammatory Cytokine Interleukin-1β (IL-1β) in a Bovine Chondrocyte Inflammation ModelRobert Ossendorff0Sarah Kurth1Su Wang2Max Jaenisch3Elio Assaf4Sebastian Scheidt5Kristian Welle6Christof Burger7Dieter C. Wirtz8Andreas C. Strauss9Frank A. Schildberg10Department of Orthopedics and Trauma Surgery, University Hospital Bonn, 53127 Bonn, GermanyDepartment of Orthopedics and Trauma Surgery, University Hospital Bonn, 53127 Bonn, GermanyDepartment of Orthopedics and Trauma Surgery, University Hospital Bonn, 53127 Bonn, GermanyDepartment of Orthopedics and Trauma Surgery, University Hospital Bonn, 53127 Bonn, GermanyDepartment of Orthopedics and Trauma Surgery, University Hospital Bonn, 53127 Bonn, GermanyDepartment of Orthopedics and Trauma Surgery, University Hospital Bonn, 53127 Bonn, GermanyDepartment of Orthopedics and Trauma Surgery, University Hospital Bonn, 53127 Bonn, GermanyDepartment of Orthopedics and Trauma Surgery, University Hospital Bonn, 53127 Bonn, GermanyDepartment of Orthopedics and Trauma Surgery, University Hospital Bonn, 53127 Bonn, GermanyDepartment of Orthopedics and Trauma Surgery, University Hospital Bonn, 53127 Bonn, GermanyDepartment of Orthopedics and Trauma Surgery, University Hospital Bonn, 53127 Bonn, GermanyInflammation models with the proinflammatory cytokine interleukin-1β (IL-1β) are widely used in the in vitro investigation of new therapeutic approaches for osteoarthritis (OA). The aim of this study was to systematically analyze the influence of IL-1β in a 3D chondral pellet culture model. Bovine articular chondrocytes were cultured to passage 3 and then placed in pellet culture. Titration of IL-1β (100–0.1 ng/mL) was performed with both human and bovine recombinant protein in chondrocyte culture for 2 weeks. Gene expression of anabolic (collagen 2, aggrecan, cartilage oligomeric protein (COMP), proteoglycan-4 (PRG-4)), catabolic matrix metallo proteinases (MMP-3, MMP-13), dedifferentiation (collagen 1) markers and inflammatory cytokines IL-6 and IL-8 was determined. Analysis of the cell culture medium was performed for the inflammatory markers IL-6 and nitric oxide (NO). In general, the influence of IL-1β was shown by a decrease in the expression of anabolic markers (collagen 2, aggrecan, PRG-4), whereas the catabolic markers MMP-3 and MMP-13 as well as the inflammatory markers IL-6 and IL-8 were significantly increased. This was observed both at the early time point (day 4) and at the late time point (day 14). The described inflammatory effects were confirmed by increased concentration-dependent release of NO and IL-6. The threshold concentration for a detectable effect compared to control differed between groups, but was reached earlier by homologous application of IL-1β. This study provides a systematic evaluation of IL-1β-specific effects on chondrocytes in a 3D pellet culture model, which is highly relevant for comparisons of studies in OA-specific drug development.https://www.mdpi.com/2073-4409/14/1/30IL-1βinflammation modelcartilagechondrocytecytokinebovine
spellingShingle Robert Ossendorff
Sarah Kurth
Su Wang
Max Jaenisch
Elio Assaf
Sebastian Scheidt
Kristian Welle
Christof Burger
Dieter C. Wirtz
Andreas C. Strauss
Frank A. Schildberg
Comparison of Concentration- and Homology-Dependent Effects of the Proinflammatory Cytokine Interleukin-1β (IL-1β) in a Bovine Chondrocyte Inflammation Model
Cells
IL-1β
inflammation model
cartilage
chondrocyte
cytokine
bovine
title Comparison of Concentration- and Homology-Dependent Effects of the Proinflammatory Cytokine Interleukin-1β (IL-1β) in a Bovine Chondrocyte Inflammation Model
title_full Comparison of Concentration- and Homology-Dependent Effects of the Proinflammatory Cytokine Interleukin-1β (IL-1β) in a Bovine Chondrocyte Inflammation Model
title_fullStr Comparison of Concentration- and Homology-Dependent Effects of the Proinflammatory Cytokine Interleukin-1β (IL-1β) in a Bovine Chondrocyte Inflammation Model
title_full_unstemmed Comparison of Concentration- and Homology-Dependent Effects of the Proinflammatory Cytokine Interleukin-1β (IL-1β) in a Bovine Chondrocyte Inflammation Model
title_short Comparison of Concentration- and Homology-Dependent Effects of the Proinflammatory Cytokine Interleukin-1β (IL-1β) in a Bovine Chondrocyte Inflammation Model
title_sort comparison of concentration and homology dependent effects of the proinflammatory cytokine interleukin 1β il 1β in a bovine chondrocyte inflammation model
topic IL-1β
inflammation model
cartilage
chondrocyte
cytokine
bovine
url https://www.mdpi.com/2073-4409/14/1/30
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