Tendon-regulating and bone-setting manipulation promotes the recovery of synovial inflammation in rabbits with knee osteoarthritis via the TLR4–MyD88–NF-κB signaling pathway

Abstract

Background: The aim of this study was to clarify the mechanism of tendon-regulating and bone-setting manipulation in the treatment of knee osteoarthritis (KOA).Methods: 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.Results: 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.Conclusions: 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.

Effect of Traditional Chinese Non-Pharmacological Therapies on Knee Osteoarthritis: A Narrative Review of Clinical Application and Mechanism

“…What’s more, Tuina can downregulate the levels of TLR4, MyD88, and NF-κB in the synovial tissue, and the contents of IL-1β, IL-6, and TNF-α in synovial fluid. 98 …”

“… Wu et al 97 EA Rabbits Downregulating the expression of IL-1β, IL-6, TNF-α, MMP-3, IKK-β, and NF-κB p65 in synovial fluid. Jin et al 98 Tuina Rabbits (1) Downregulating the levels of TLR4, MyD88, and NF-κB in the synovial tissue. (2) Downregulating the contents of IL-1β, IL-6, and TNF-α in synovial fluid.…”

“…What's more, Tuina can downregulate the levels of TLR4, MyD88, and NF-κB in the synovial tissue, and the contents of IL-1β, IL-6, and TNF-α in synovial fluid. 98 Traditional Chinese non-pharmacological therapy reduces synovitis by modulating macrophage polarization. Synovial macrophages are important inflammatory cells in joint synovium, and their different polarization states play an important role in the development of KOA.…”

“…Jin et al 98 Tuina Rabbits (1) Downregulating the levels of TLR4, MyD88, and NF-κB in the synovial tissue.…”