Molecular treatments to reduce catabolic effects in human meniscus explant models
Objectives: 1. To validate catabolic meniscus explant models induced by cytokines: interleukin-6 + interleukin-6 receptor + tumor necrosis factor alpha (IL6/TNF) and oncostatin M + tumor necrosis factor alpha (OSM/TNF). 2. To evaluate three potential anti-catabolic treatments: i) dexamethasone...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-09-01
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| Series: | Osteoarthritis and Cartilage Open |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2665913125000548 |
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| author | Amanda Sjögren Karin Lindblom Aleksandra Turkiewicz Martin Englund Patrik Önnerfjord |
| author_facet | Amanda Sjögren Karin Lindblom Aleksandra Turkiewicz Martin Englund Patrik Önnerfjord |
| author_sort | Amanda Sjögren |
| collection | DOAJ |
| description | Objectives: 1. To validate catabolic meniscus explant models induced by cytokines: interleukin-6 + interleukin-6 receptor + tumor necrosis factor alpha (IL6/TNF) and oncostatin M + tumor necrosis factor alpha (OSM/TNF). 2. To evaluate three potential anti-catabolic treatments: i) dexamethasone (DEX), ii) a Link-N peptide (Link-N) and iii) a peptide from chondroadherin (CKF). Design: Healthy lateral menisci from deceased donors (n = 6; age = 25–70 years, 4 males, 2 females), were sliced and randomized for experimental groups (combinations of the catabolic models and anti-catabolic treatments) and a control group. Culture media were analyzed, every third day until day 18, by mass spectrometry-based proteomics. Linear mixed effect models were used to estimate differences in protein abundances between groups. Results: A total of 662 proteins were identified in all menisci. Cytokine-treated meniscus explant models showed increased release of osteoarthritis-related proteins such as matrix metalloproteinases (MMPs). For example, MMP1: IL6/TNF vs. ctrl; log2 fold-change 2.2 95 % confidence interval [1.8, 2.5] and OSM/TNF vs. ctrl; log2 fold-change 2.8 [2.4, 3.1]. There was no treatment effect in explant meniscus with the addition of either Link-N or CKF. Treatment effects were, however, evident with the addition of DEX. For example, MMP1: IL6/TNF + DEX vs. ctrl; log2 fold-change −1.8 [-2.2, −1.4] and OSM/TNF + DEX vs. ctrl; log2 fold-change −0.3 [-0.7, 0.04]. Conclusion: We confirmed that both catabolic models induce changes in osteoarthritis-related proteins. DEX treatment is effective in mitigating the catabolic response in meniscus explant models and may be further explored for its effects in the treatment of meniscus degeneration. |
| format | Article |
| id | doaj-art-e5e01ed82871407fb3dac6f59fa807cb |
| institution | Kabale University |
| issn | 2665-9131 |
| language | English |
| publishDate | 2025-09-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Osteoarthritis and Cartilage Open |
| spelling | doaj-art-e5e01ed82871407fb3dac6f59fa807cb2025-08-20T03:52:43ZengElsevierOsteoarthritis and Cartilage Open2665-91312025-09-017310061810.1016/j.ocarto.2025.100618Molecular treatments to reduce catabolic effects in human meniscus explant modelsAmanda Sjögren0Karin Lindblom1Aleksandra Turkiewicz2Martin Englund3Patrik Önnerfjord4Lund University, Faculty of Medicine, Department of Clinical Sciences Lund, Orthopaedics, Clinical Epidemiology Unit, Lund, Sweden; Corresponding author. Lund University, Faculty of Medicine, Department of Clinical Sciences, Lund, Sweden.Lund University, Faculty of Medicine, Department of Clinical Sciences Lund, Section for Rheumatology and Molecular Skeletal Biology, Lund, SwedenLund University, Faculty of Medicine, Department of Clinical Sciences Lund, Orthopaedics, Clinical Epidemiology Unit, Lund, SwedenLund University, Faculty of Medicine, Department of Clinical Sciences Lund, Orthopaedics, Clinical Epidemiology Unit, Lund, SwedenLund University, Faculty of Medicine, Department of Clinical Sciences Lund, Section for Rheumatology and Molecular Skeletal Biology, Lund, SwedenObjectives: 1. To validate catabolic meniscus explant models induced by cytokines: interleukin-6 + interleukin-6 receptor + tumor necrosis factor alpha (IL6/TNF) and oncostatin M + tumor necrosis factor alpha (OSM/TNF). 2. To evaluate three potential anti-catabolic treatments: i) dexamethasone (DEX), ii) a Link-N peptide (Link-N) and iii) a peptide from chondroadherin (CKF). Design: Healthy lateral menisci from deceased donors (n = 6; age = 25–70 years, 4 males, 2 females), were sliced and randomized for experimental groups (combinations of the catabolic models and anti-catabolic treatments) and a control group. Culture media were analyzed, every third day until day 18, by mass spectrometry-based proteomics. Linear mixed effect models were used to estimate differences in protein abundances between groups. Results: A total of 662 proteins were identified in all menisci. Cytokine-treated meniscus explant models showed increased release of osteoarthritis-related proteins such as matrix metalloproteinases (MMPs). For example, MMP1: IL6/TNF vs. ctrl; log2 fold-change 2.2 95 % confidence interval [1.8, 2.5] and OSM/TNF vs. ctrl; log2 fold-change 2.8 [2.4, 3.1]. There was no treatment effect in explant meniscus with the addition of either Link-N or CKF. Treatment effects were, however, evident with the addition of DEX. For example, MMP1: IL6/TNF + DEX vs. ctrl; log2 fold-change −1.8 [-2.2, −1.4] and OSM/TNF + DEX vs. ctrl; log2 fold-change −0.3 [-0.7, 0.04]. Conclusion: We confirmed that both catabolic models induce changes in osteoarthritis-related proteins. DEX treatment is effective in mitigating the catabolic response in meniscus explant models and may be further explored for its effects in the treatment of meniscus degeneration.http://www.sciencedirect.com/science/article/pii/S2665913125000548MeniscusExplant modelHuman tissueProteomicsOsteoarthritis |
| spellingShingle | Amanda Sjögren Karin Lindblom Aleksandra Turkiewicz Martin Englund Patrik Önnerfjord Molecular treatments to reduce catabolic effects in human meniscus explant models Osteoarthritis and Cartilage Open Meniscus Explant model Human tissue Proteomics Osteoarthritis |
| title | Molecular treatments to reduce catabolic effects in human meniscus explant models |
| title_full | Molecular treatments to reduce catabolic effects in human meniscus explant models |
| title_fullStr | Molecular treatments to reduce catabolic effects in human meniscus explant models |
| title_full_unstemmed | Molecular treatments to reduce catabolic effects in human meniscus explant models |
| title_short | Molecular treatments to reduce catabolic effects in human meniscus explant models |
| title_sort | molecular treatments to reduce catabolic effects in human meniscus explant models |
| topic | Meniscus Explant model Human tissue Proteomics Osteoarthritis |
| url | http://www.sciencedirect.com/science/article/pii/S2665913125000548 |
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