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单独或联合使用时,透明质酸和硫酸软骨素通过抑制NF-κB途径减轻骨关节炎中的细胞外基质降解。

Alone or in combination, hyaluronic acid and chondroitin sulfate alleviate ECM degradation in osteoarthritis by inhibiting the NF-κB pathway.

作者信息

Ma Yiran, Yang Xin, Jiang Min, Ye Wangjuan, Qin Hong, Tan Songwen

机构信息

Aunobel pty Ltd Nutrition and health research institute, Strathfield, 2135, NSW, Australia.

Monash Suzhou Research Institute, Monash University, Suzhou, 215000, Jiangsu, China.

出版信息

J Orthop Surg Res. 2025 Jan 4;20(1):11. doi: 10.1186/s13018-024-05411-6.

DOI:10.1186/s13018-024-05411-6
PMID:39754163
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11699666/
Abstract

BACKGROUNDS

Osteoarthritis (OA) significantly impacts the elderly, leading to disability and decreased quality of life. While hyaluronic acid (HA) and chondroitin sulfate (CS) are recognized for their therapeutic potential in OA, their effects on extracellular matrix (ECM) degradation are not well understood. This study investigates the impact of HA and CS, individually and combined, on ECM degradation in OA and the underlying mechanisms.

METHODS

OA was modeled in rats through anterior cruciate ligament transection and in cells using IL-1β pretreatment. Treatments included HA and CS, alone or combined, with and without PMA (an NF-κB pathway activator). Cartilage tissue was analyzed using HE and Saffron O-fast green staining, with degradation assessed via the OARSI score. Inflammatory factors were measured by ELISA, and ECM-related proteins were detected by immunohistochemistry, immunofluorescence, and Western blotting. Chondrocyte viability was assessed using CCK8.

RESULTS

HA and CS treatments significantly reduced cartilage damage, decreased inflammatory factor release, alleviated ECM degradation, and inhibited NF-κB pathway activation compared to the OA group (P < 0.05). The combination of HA and CS further enhanced these therapeutic effects (P < 0.05). However, these benefits were reversed when PMA was introduced (P < 0.05).

CONCLUSION

HA and CS, whether used alone or in combination, mitigate ECM degradation in osteoarthritis by inhibiting the NF-κB pathway, offering potential therapeutic benefits for OA management.

摘要

背景

骨关节炎(OA)对老年人有显著影响,会导致残疾并降低生活质量。虽然透明质酸(HA)和硫酸软骨素(CS)在OA治疗方面的潜力已得到认可,但其对细胞外基质(ECM)降解的影响尚不清楚。本研究调查了HA和CS单独及联合使用对OA中ECM降解的影响及其潜在机制。

方法

通过切断大鼠前交叉韧带建立OA模型,并使用白细胞介素-1β预处理细胞。治疗包括单独或联合使用HA和CS,以及添加或不添加佛波酯(PMA,一种核因子κB通路激活剂)。使用苏木精-伊红(HE)和番红O-固绿染色分析软骨组织,通过骨关节炎研究学会国际(OARSI)评分评估降解情况。通过酶联免疫吸附测定(ELISA)测量炎症因子,通过免疫组织化学、免疫荧光和蛋白质免疫印迹法检测与ECM相关的蛋白质。使用细胞计数试剂盒-8(CCK8)评估软骨细胞活力。

结果

与OA组相比,HA和CS治疗显著减少了软骨损伤,降低了炎症因子释放,减轻了ECM降解,并抑制了核因子κB通路激活(P < 0.05)。HA和CS联合使用进一步增强了这些治疗效果(P < 0.05)。然而,当引入PMA时,这些益处被逆转(P < 0.05)。

结论

HA和CS单独或联合使用,均可通过抑制核因子κB通路减轻骨关节炎中的ECM降解,为OA的管理提供潜在的治疗益处。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6dbf/11699666/782f67b1dd53/13018_2024_5411_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6dbf/11699666/53c7ee1bff70/13018_2024_5411_Fig1_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6dbf/11699666/aed13ef73c9b/13018_2024_5411_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6dbf/11699666/dffbd152f238/13018_2024_5411_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6dbf/11699666/f070c055e628/13018_2024_5411_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6dbf/11699666/782f67b1dd53/13018_2024_5411_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6dbf/11699666/53c7ee1bff70/13018_2024_5411_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6dbf/11699666/641b1d9bd13e/13018_2024_5411_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6dbf/11699666/aed13ef73c9b/13018_2024_5411_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6dbf/11699666/dffbd152f238/13018_2024_5411_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6dbf/11699666/f070c055e628/13018_2024_5411_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6dbf/11699666/782f67b1dd53/13018_2024_5411_Fig6_HTML.jpg

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