Mechanism Study on the Effect of Dihuang Gutongkang Capsules Improving Knee Osteoarthritis in Rats by Regulating the MYD88/NF - κ B/NLRP3 Signaling Pathway and Reducing Osteoclast Differentiation

Abstract

Objective: This study aimed to investigate the effects of Dihuang Gutong Kang capsule on osteoclast differentiation in knee osteoarthritis (KOA) rats and its mechanism via the MYD88/NF-κB/NLRP3 signaling pathway. Methods: A KOA rat model was established by sodium monoiodoacetate (MIA) induction. Successfully modeled rats were randomized into the model group, low-dose Dihuang Gutong Kang capsule group (16.2 g/kg/d), high-dose Dihuang Gutong Kang capsule group (32.4 g/kg/d), celecoxib group (0.52 g/kg/d), and a blank control group. Cartilage pathology was evaluated by H&E staining; mRNA levels of inflammatory cytokines (IL-6, TNF-α) were measured via qPCR; osteoclast activity was analyzed by TRAP staining; and co-expression of TRAP with MYD88, NLRP3, and p-p65 NF-κB was observed using immunofluorescence co-staining. Results: Compared with the blank group, the model group exhibited severe cartilage damage (P<0.001), upregulated IL-6 and TNF-α expression (P<0.001), increased TRAP-positive osteoclasts (P<0.001), and enhanced co-expression of TRAP with MYD88/NLRP3/p-p65 NF-κB (P<0.001). In contrast, high-dose DIHUANG GUTONG KANG CAPSULE significantly alleviated cartilage defects and inflammatory infiltration (P<0.01), reduced IL-6 and TNF-α levels (P<0.001), suppressed TRAP-positive osteoclast numbers (P<0.001), and decreased TRAP+MYD88/NLRP3/p-p65 co-expression (P<0.001) compared to the model group. Conclusion: Dihuang Gutong Kang capsule attenuates osteoclast activation and inflammatory responses by inhibiting the MYD88/NF-κB/NLRP3 pathway, thereby ameliorating KOA progression.