补肾痹通方靶向TLR4/非规范NF-κB通路可增强骨关节炎中基于BMSCs的软骨修复

Targeting TLR4/non-canonical NF-κB pathway by Bushen Bitong recipe enhances BMSCs-based cartilage repair in osteoarthritis.

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摘要(中文译文)

补肾通痹方(BSBT)是一种临床上用于治疗骨关节炎的中药,而骨髓间充质基质细胞(BMSCs)疗法因其免疫调节和抗炎特性而日益得到应用。然而,二者联合应用对骨关节炎的作用尚未被研究。在本研究中,含BSBT血清逆转了IL-1β诱导的细胞凋亡,并提高了BMSCs和软骨细胞的活力。CCK-8和Transwell实验显示,BSBT与BMSCs联合处理进一步增强了软骨细胞的活力和迁移能力。在体内,X射线成像和组织学染色(H&E和甲苯胺蓝)表明,联合治疗保留了关节间隙,减少了骨赘形成,并维持了软骨结构,软骨细胞排列更为有序。在机制层面,TUNEL染色显示,与骨关节炎对照相比,联合治疗显著减少了关节软骨中的软骨细胞凋亡。这些发现与Western blot分析一致,后者显示联合处理后促凋亡蛋白Bax和cleaved caspase-3的表达降低。免疫荧光染色进一步证明,组织水平上TLR4、MyD88和磷酸化RelB(-RelB)的表达降低,表明TLR4/非经典NF-κB信号传导减弱。Western blot和ELISA分析支持了这些观察结果,显示TLR4/p-RelB受到抑制,同时促炎细胞因子和氧化应激降低。总体而言,这些结果表明,BSBT和BMSCs通过减少软骨细胞凋亡和抑制炎症信号传导,对软骨发挥协同保护作用,代表了一种有前景的膝骨关节炎治疗策略。

Abstract

Bushen Bitong Recipe (BSBT) is a traditional Chinese medicine used clinically for osteoarthritis, while bone marrow mesenchymal stromal cell (BMSCs) therapy is increasingly applied for its immunomodulatory and anti-inflammatory properties. However, their combined effects on osteoarthritis have not been investigated. In this study, BSBT containing serum reversed IL-1β induced apoptosis and improved the viability of BMSCs and chondrocytes. Co-treatment with BSBT and BMSCs further enhanced chondrocyte viability and migration, as shown by CCK-8 and Transwell assays. In vivo, X-ray imaging and histological staining (H&E and toluidine blue) demonstrated that the combined therapy preserved joint space, reduced osteophyte formation, and maintained cartilage structure with a more organized arrangement of chondrocytes. At the mechanistic level, TUNEL staining revealed that the combined treatment markedly reduced chondrocyte apoptosis in articular cartilage compared with osteoarthritic controls. These findings were consistent with Western blot analysis, which showed decreased expression of pro-apoptotic proteins Bax and cleaved caspase-3 after co-treatment. Immunofluorescence staining further demonstrated reduced tissue level expression of TLR4, MyD88, and phosphorylated RelB (-RelB), indicating attenuation of TLR4/non-canonical NF-κB signaling. Western blot and ELISA analyses supported these observations, showing suppression of TLR4/p-RelB and a concomitant decrease in pro-inflammatory cytokines and oxidative stress. Overall, these results suggest that BSBT and BMSCs exert synergistic protective effects on cartilage by reducing chondrocyte apoptosis and dampening inflammatory signaling, representing a promising therapeutic strategy for knee osteoarthritis.

如何引用

AMA

Wenyuan Xiang, Cheng Xiang, Atikul Islam, Lin Yi, Zhengxiao Ouyang, Rui Fang. Targeting TLR4/non-canonical NF-κB pathway by Bushen Bitong recipe enhances BMSCs-based cartilage repair in osteoarthritis.. Biochemistry and biophysics reports. 2026; doi:10.1016/j.bbrep.2026.102632.

APA

Wenyuan Xiang, Cheng Xiang, Atikul Islam, Lin Yi, Zhengxiao Ouyang, Rui Fang (2026). Targeting TLR4/non-canonical NF-κB pathway by Bushen Bitong recipe enhances BMSCs-based cartilage repair in osteoarthritis.. Biochemistry and biophysics reports. https://doi.org/10.1016/j.bbrep.2026.102632

GB/T 7714

Wenyuan Xiang, Cheng Xiang, Atikul Islam, Lin Yi, Zhengxiao Ouyang, Rui Fang. Targeting TLR4/non-canonical NF-κB pathway by Bushen Bitong recipe enhances BMSCs-based cartilage repair in osteoarthritis.[J]. Biochemistry and biophysics reports, 2026 doi:10.1016/j.bbrep.2026.102632.

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