ArticleOsteoarthritis and cartilage open2025
Molecular treatments to reduce catabolic effects in human meniscus explant models.
Article in Osteoarthritis and cartilage open, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
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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