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血清细胞外囊泡的跨膜蛋白谱反映了膝骨关节炎的功能障碍和疼痛感知。

Tetraspanin profiles of serum extracellular vesicles reflect functional limitations and pain perception in knee osteoarthritis.

机构信息

Institute of Biomedicine, School of Medicine, Faculty of Health Sciences, University of Eastern Finland, Kuopio, Finland.

Department of Environmental and Biological Sciences, Faculty of Science, Forestry and Technology, University of Eastern Finland, Joensuu, Finland.

出版信息

Arthritis Res Ther. 2024 Jan 22;26(1):33. doi: 10.1186/s13075-023-03234-0.

DOI:10.1186/s13075-023-03234-0
PMID:38254142
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10801950/
Abstract

BACKGROUND

Emerging evidence suggests that extracellular vesicles (EVs) can play roles in inflammatory processes and joint degradation in primary osteoarthritis (OA), a common age-associated joint disease. EV subpopulations express tetraspanins and platelet markers that may reflect OA pathogenesis. The present study investigated the associations between these EV surface markers and articular cartilage degradation, subjectively and objectively assessed pain, and functional limitations in primary knee OA (KOA).

METHODS

Serum EVs were determined by high-sensitivity flow cytometry (large CD61 EVs) and single particle interferometric reflectance imaging sensor (small CD41, CD63, CD81, and CD9 EVs) from end-stage KOA patients and controls (n = 8 per group). Knee pain and physical functions were assessed with several health- and pain-related questionnaires, established measurements of physical medicine, and neuromuscular examination. The obtained data were analyzed using supervised and unsupervised univariate and multivariate models.

RESULTS

With the combined dataset of cartilage thickness, knee function, pain, sensation, and EV molecular signatures, we identified highly correlated groups of variables and found several EV markers that were statistically significant predictors of pain, physical limitations, and other aspects of well-being for KOA patients, for instance CD41/CD63/CD9 small EVs associated with the range of motion of the knee, physical performance, and pain sensitivity.

CONCLUSIONS

Particular serum EV subpopulations showed clear associations with KOA pain and functional limitations, suggesting that their implications in OA pathophysiology warrant further study.

摘要

背景

越来越多的证据表明,细胞外囊泡(EVs)在原发性骨关节炎(OA)的炎症过程和关节降解中发挥作用,OA 是一种常见的与年龄相关的关节疾病。EV 亚群表达四跨膜蛋白和血小板标志物,这些标志物可能反映 OA 的发病机制。本研究探讨了这些 EV 表面标志物与关节软骨降解、主观和客观评估的疼痛以及原发性膝骨关节炎(KOA)的功能障碍之间的关系。

方法

通过高灵敏度流式细胞术(大 CD61 EVs)和单颗粒干涉反射成像传感器(小 CD41、CD63、CD81 和 CD9 EVs)从终末期 KOA 患者和对照组(每组 8 例)中确定血清 EVs。使用几种健康和疼痛相关的问卷、物理医学的既定测量和神经肌肉检查评估膝关节疼痛和身体功能。使用有监督和无监督的单变量和多变量模型分析获得的数据。

结果

结合软骨厚度、膝关节功能、疼痛、感觉和 EV 分子特征的数据集,我们确定了高度相关的变量组,并发现了几个 EV 标志物,这些标志物是 KOA 患者疼痛、身体限制和其他方面的幸福感的统计学显著预测因子,例如与膝关节活动度、身体表现和疼痛敏感性相关的小 EVs CD41/CD63/CD9。

结论

特定的血清 EV 亚群与 KOA 疼痛和功能障碍明显相关,表明它们在 OA 病理生理学中的意义值得进一步研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc75/10801950/82c6e47528a9/13075_2023_3234_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc75/10801950/a098281ec20e/13075_2023_3234_Fig1_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc75/10801950/82c6e47528a9/13075_2023_3234_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc75/10801950/a098281ec20e/13075_2023_3234_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc75/10801950/9b8aaee6c82f/13075_2023_3234_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc75/10801950/5b0f5d7fe87b/13075_2023_3234_Fig3_HTML.jpg
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