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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| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-09-01
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| Series: | Osteoarthritis and Cartilage Open |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2665913125000548 |
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| Summary: | 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. |
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| ISSN: | 2665-9131 |