橙皮素减轻骨关节炎模型小鼠软骨损伤

doi:10.16352/j.issn.1001-6325.2026.09.1167

基础医学与临床 ›› 2026, Vol. 46 ›› Issue (9): 1167-1174.doi: 10.16352/j.issn.1001-6325.2026.09.1167

橙皮素减轻骨关节炎模型小鼠软骨损伤

张自强^1,2,3, 王杰², 关云博^2,3, 孙笑非³, 李健⁴, 翁土军², 王祖强^1,2,3*

1.安徽医科大学第二附属医院, 安徽合肥 230032;
2.中国人民解放军总医院第四医学中心骨科医学部,北京 100037;
3.中国人民解放军总医院第六医学中心骨科,北京 100048;
4.赣南医科大学第一附属医院, 江西赣州 341000

收稿日期:2026-04-28 修回日期:2026-06-12 出版日期:2026-09-05 发布日期:2026-08-18
通讯作者: ^*wangzqtmmu@hotmail.com
基金资助:
国家自然科学基金(82102594)

Hesperetin attenuates cartilage damage in mouse models of osteoarthritis

ZHANG Ziqiang^1,2,3, WANG Jie², GUAN Yunbo^2,3, SUN Xiaofei³, LI Jian⁴, WENG Tujun², WANG Zuqiang^1,2,3*

1. The Second Affiliated Hospital of Anhui Medical University, Hefei 230032;
2. Senior Department of Orthopedics, the Fourth Medical Center, General Hospital of Chinese PLA, Beijing 100037;
3. Department of Orthopedics, the Sixth Medical Center, General Hospital of Chinese PLA, Beijing 100048;
4. The First Affiliated Hospital of Gannan Medical University, Ganzhou 341000, China

Received:2026-04-28 Revised:2026-06-12 Online:2026-09-05 Published:2026-08-18
Contact: ^*wangzqtmmu@hotmail.com

摘要/Abstract

摘要： 目的评价橙皮素(HST)对小鼠内侧半月板不稳定(DMM)骨关节炎软骨损伤的治疗作用,并通过骨髓间充质干细胞(BM-MSCs)成软骨诱导模型和白介素 1β(IL-1β)诱导的软骨细胞炎症模型,从促进成软骨分化和抑制软骨细胞炎症反应两个方面探讨其可能机制。方法 1)细胞实验:体外采用CCK-8法评价橙皮素对BM-MSCs活力的影响;建立 BM-MSCs 成软骨诱导模型,并采用Ⅱ型胶原蛋白(COL2)免疫荧光染色评价成软骨分化水平;建立IL-1β诱导的软骨细胞炎症模型,并采用实时荧光定量PCR检测炎症相关基因表达。 2)动物实验:建立小鼠DMM骨关节炎模型,给予关节腔注射橙皮素干预,通过步态分析、组织学染色及骨关节炎研究学会国际(OARSI)评分评价其作用。结果在0.4~10 μmol/L浓度范围内,橙皮素对BM-MSCs活力无明显影响, 而50 μmol/L橙皮素可降低BM-MSCs活力(P＜0.05)。与对照组比较,橙皮素可增强BM-MSCs成软骨诱导过程中COL2表达(P＜0.05)。在IL-1β刺激的软骨细胞中,橙皮素可下调IL-1β、IL-6和TNF-α mRNA表达水平(P＜0.05)。在DMM小鼠模型中,橙皮素干预后小鼠的步态异常得到改善,关节软骨损伤减轻,OARSI评分降低(P＜0.05)。结论在DMM 骨关节炎模型小鼠中,橙皮素可减轻软骨损伤,其作用可能与促进 BM-MSCs 成软骨分化及抑制炎性刺激下软骨细胞炎症相关基因表达有关。

关键词: 橙皮素, 骨髓间充质干细胞, 成软骨分化, 软骨细胞, 骨关节炎

Abstract: Objective To evaluate the effect of hesperetin (HST) on cartilage damage in mouse models of destabilization in medial meniscus (DMM)-induced osteoarthritis, and to explore mechanisms. Methods 1)In vitro experiments: CCK-8 assay was used to evaluate the effect of hesperetin on bone marrow mesenchymal stem cells(BM-MSCs) viability. BM-MSCs chondrogenic induction model was established and chondrogenic differentiation was evaluated by type Ⅱ collagen(COL2)immunofluorescence staining microscopy; An IL-1β-induced chondrocyte inflammatory model was established, and real-time quantitative PCR was used to detect the expression of inflammation-related genes. 2) Animal experiments:A mouse DMM model of osteoarthritis was established, and hesperetin was administered by intra-articular injection. Gait analysis, histological staining, and Osteoarthritis Research Society International (OARSI) scoring were used to evaluate its effects. Results Within the concentration range of 0.4-10 μmol/L, hesperetin had no significant effect on BM-MSCs viability, whereas 50 μmol/L hesperetin reduced BM-MSCs viability(P＜0.05). Compared to the control group, hesperetin enhanced COL2 expression during BM-MSCs chondrogenic induction(P＜0.05). In IL-1β-stimulated chondrocytes, hesperetin downregulated the mRNA expression levels of IL-1β, IL-6, and TNF-α(P＜0.05). In the DMM mouse model, hesperetin improved gait abnormalities, alleviated cartilage damage and reduced OARSI scores(P＜0.05). Conclusions In osteoarthritis of DMM mouse models, hesperetin alleviated cartilage damage. Its effects may be associated with the promotion of BM-MSCs chondrogenic differentiation and inhibition of inflammation-related gene expression in chondrocytes under inflammatory stimulation.

Key words: hesperetin, bone marrow mesenchymal stem cell, chondrogenic differentiation, chondrocyte, osteoarthritis

中图分类号:

R684.3

张自强, 王杰, 关云博, 孙笑非, 李健, 翁土军, 王祖强. 橙皮素减轻骨关节炎模型小鼠软骨损伤[J]. 基础医学与临床, 2026, 46(9): 1167-1174.

ZHANG Ziqiang, WANG Jie, GUAN Yunbo, SUN Xiaofei, LI Jian, WENG Tujun, WANG Zuqiang. Hesperetin attenuates cartilage damage in mouse models of osteoarthritis[J]. Basic & Clinical Medicine, 2026, 46(9): 1167-1174.

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橙皮素减轻骨关节炎模型小鼠软骨损伤

Hesperetin attenuates cartilage damage in mouse models of osteoarthritis

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