减少人类半月板外植体模型分解代谢作用的分子治疗

Osteoarthritis and cartilage open Pub Date : 2025-04-30 DOI:10.1016/j.ocarto.2025.100618

Amanda Sjögren , Karin Lindblom , Aleksandra Turkiewicz , Martin Englund , Patrik Önnerfjord

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引用次数: 0

摘要

Objectives1。验证细胞因子：白细胞介素-6 +白细胞介素-6受体+肿瘤坏死因子α (il -6 /TNF)和肿瘤抑制素M +肿瘤坏死因子α (OSM/TNF)诱导的分解代谢半月板外植体模型。2. 评估三种潜在的抗分解代谢治疗方法：1)地塞米松（DEX）， 2)链接- n肽（Link-N）和3)软骨粘附素（CKF）肽。设计来自已故供体的健康外侧半月板(n = 6；年龄25 ~ 70岁，男4例，女2例)，切片后随机分为实验组（分解代谢模型联合抗分解代谢治疗组）和对照组。通过基于质谱的蛋白质组学，每隔3天对培养基进行分析，直到第18天。线性混合效应模型用于估计组间蛋白质丰度的差异。结果在所有半月板中共鉴定出662个蛋白。细胞因子处理的半月板外植体模型显示骨关节炎相关蛋白如基质金属蛋白酶（MMPs）的释放增加。例如，MMP1: IL6/TNF vs. ctrl；log2 - fold change 2.2 95%置信区间[1.8,2.5]和OSM/TNF与对照；Log2 - fold change 2.8[2.4, 3.1]。添加Link-N或CKF对外植体半月板均无治疗效果。然而，在添加DEX后，治疗效果明显。例如，MMP1: IL6/TNF + DEX vs. ctrl；log2 - fold change - 1.8[-2.2, - 1.4]和OSM/TNF + DEX与对照组比较；Log2 - fold-change−0.3[-0.7,0.04]。结论两种分解代谢模型均可引起骨关节炎相关蛋白的改变。DEX治疗能有效减轻半月板外植体模型的分解代谢反应，其治疗半月板退行性变的效果有待进一步探讨。

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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 (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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来源期刊

Osteoarthritis and cartilage open Orthopedics, Sports Medicine and Rehabilitation

CiteScore

3.30

自引率

0.00%

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