Mechanistic study on the reduction of TNF-α and β-CTX levels in RA patients by moxibustion combined with western medication through regulation of the Wnt/β-catenin pathway.

Background and aims: The pathological core of rheumatoid arthritis (RA) is progressive bone destruction driven by chronic inflammation. The Wnt/β-catenin signaling pathway plays a key regulatory role in bone metabolism, but it is disrupted by the inflammatory environment in RA. This study investigates the mechanism by which moxibustion combined with conventional Western medicine modulates the Wnt/β-catenin signaling pathway to coordinate inflammation and bone metabolism in rheumatoid arthritis (RA). Methods: This study randomly assigned 70 patients to a moxibustion group (n=35) and a control group (n=35). The control group received oral methotrexate (10 mg/week) combined with folic acid (10 mg/week). The moxibustion group received the same medication as the control group plus moxibustion therapy primarily targeting Zusanli (ST36), and Ashi points, administered three times weekly for a 4-week course. Clinical symptoms and laboratory parameters were compared between groups, and serum levels of tumor necrosis factor-alpha (TNF-α), interleukin-17A (IL-17A), wingless-type MMTV integration site family member 3A (WNT3A), low-density lipoprotein receptor-related protein 6 (LRP-6), glycogen synthase kinase-3 beta (GSK-3β), β-catenin, osteoprotegerin (OPG), and beta-C-terminal telopeptide of type I collagen (β-CTX) were measured. Results: Compared with the conventional control group alone, moxibustion combined therapy significantly improved clinical symptoms in RA patients (P<0.05). Mechanistically, the moxibustion group simultaneously downregulated serum proinflammatory factors (TNF-α, IL-17A) and bone resorption marker β-CTX, suppressed abnormally activated Wnt pathway molecules (WNT3A, LRP-6, β-catenin), and upregulated the bone protective factor OPG while inhibiting GSK-3β (P < 0.05 for both intra- and intergroup comparisons). Correlation analysis revealed positive correlations between β-catenin changes and those in TNF-α and WNT3A ( Conclusion: The combination of moxibustion and Western medicine effectively alleviates clinical symptoms in patients with rheumatoid arthritis and suggests a potential to delay structural damage. Its mechanism involves suppressing key inflammatory mediators TNF-α and IL-17A, thereby activating and regulating the Wnt/β-catenin signaling pathway. This modulates serum levels of OPG and β-CTX, leading to systemic improvement in bone metabolic balance and exerting a multi-target therapeutic effect.