本研究旨在澄清肌腱调节和骨定位治疗膝骨关节炎（KOA）机制。共选择30只健康特定病原体自由（SPF）新西兰白兔（雄性；体重2.0-2.5千克），分为正常对照（NC）组、KOA组和KOA + 手工治疗（MT）组，每组10只兔子。采用修改后的Hulth方法在KOA和KOA + MT组建立了KOA模型。三组兔子在相同条件下饲养8周。使用KOA的Lequesne指数评估模型兔子的行为状态；使用苏木精-伊红染色观察胫骨平台和内侧股骨髁软骨的病理形态；使用Mankin评分标准评估模型兔子的软骨形态；使用Western印迹检测模型兔子滑膜组织中Toll样受体4（TLR4）、髓样分化因子88（MyD88）和核因子κB（NF-κB）蛋白表达水平，使用酶联免疫吸附法（ELISA）方法测定模型兔子滑膜液中白细胞介素（IL）-1β、IL-6和肿瘤坏死因子α（TNF-α）的含量。与NC组相比，KOA和KOA + MT组的Lequesne指数评分、软骨组织的Mankin评分、蛋白表达和炎性因子含量均显著增加（P <0.05），并且这些值在KOA组中显著更高。显微镜观察显示，KOA和KOA + MT组的实验兔的软骨组织明显退化。与KOA组相比，KOA + MT组模型兔的Lequesne指数评分、Mankin评分、蛋白表达和炎性因子含量显著降低（P <0.05），显微镜观察显示，KOA + MT组实验兔的软骨组织退化明显改善。肌腱调节和骨定位疗法可以显著改善KOA模型兔的活动状态和运动功能，并显著抑制滑膜组织中的TLR4-MyD88-NF-κB信号通路的表达，从而减轻膝关节滑膜炎症，延缓KOA的发生和发展。2023 Annals of Translational Medicine.版权所有。

The aim of this study was to clarify the mechanism of tendon-regulating and bone-setting manipulation in the treatment of knee osteoarthritis (KOA).A total of 30 adult healthy specific pathogen-free (SPF) New Zealand white rabbits (male; weight 2.0-2.5 kg) were selected and divided into a normal control (NC) group, KOA group, and KOA + manual treatment (MT) group. Each group comprised 10 rabbits. A KOA model was established using the modified Hulth method in the KOA and KOA + MT groups. The 3 groups were fed under the same conditions for 8 weeks. The Lequesne index for KOA was used to evaluate the behavioral status of the model rabbits; hematoxylin and eosin (HE) staining was employed to observe the pathological morphology of the tibial plateau and medial femoral condyle cartilage; the Mankin scoring scale was used to evaluate the cartilage morphology of the model rabbits; Western blot was used to detect the expression levels of toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), and nuclear factor κB (NF-κB) proteins in the synovial tissue of the model rabbits; the contents of interleukin (IL)-1β, IL-6, and, tumor necrosis alpha (TNF-α) in the synovial fluid of the model rabbits were determined using the enzyme-linked immunosorbent assay (ELISA) method.Compared with those in the NC group, Lequesne index score, Mankin score of cartilage tissue, protein expression, and content of inflammatory factors were significantly increased in the KOA and KOA + MT groups (P<0.05), and these values were significantly higher in the KOA group. Microscopy showed that the cartilage tissue of the experimental rabbits in the KOA and KOA + MT groups was significantly degenerated. Compared with those in the KOA group, the Lequesne index score, Mankin score, protein expression, and inflammatory factor content of the model rabbits in the KOA + MT group were significantly reduced (P<0.05), and microscopy showed that cartilage tissue degeneration of the experimental rabbits in the KOA + MT group was significantly improved.Tendon-regulating and bone-setting manipulation can significantly improve the activity state and motor function of KOA model rabbits and significantly inhibit the expression of the TLR4-MyD88-NF-κB signaling pathway in synovial tissue, thereby reducing knee joint synovial inflammation and delaying the occurrence and development of KOA.2023 Annals of Translational Medicine. All rights reserved.