Moxibustion with Western Medication Reduces TNF-α and β-CTX in RA Patients by Modulating Wnt/β-Catenin Pathway

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by persistent synovial inflammation, progressive cartilage destruction, and irreversible bone erosion. Current standard-of-care often targets downstream inflammatory mediators, but a comprehensive approach addressing both inflammation and bone metabolism remains a significant challenge. The Wnt/β-catenin signaling pathway is crucial for bone metabolism, yet its function is often disrupted within the inflammatory milieu of RA, contributing to bone destruction. This study investigates how moxibustion, an adjunctive therapy, can modulate this pathway to coordinate inflammatory and bone metabolic responses.

This randomized controlled study enrolled 70 patients with RA, assigning n=35 to a moxibustion group and n=35 to a control group. The control group received standard oral methotrexate (10 mg/week) combined with folic acid (10 mg/week). The moxibustion group received the same conventional medication regimen plus moxibustion therapy, primarily targeting Zusanli (ST36) and Ashi points, administered three times weekly for a 4-week course. Researchers compared clinical symptoms and measured serum levels of TNF-α, IL-17A, WNT3A, LRP-6, GSK-3β, β-catenin, OPG, and β-CTX to assess inflammatory markers, Wnt pathway components, and bone turnover.

Compared to conventional Western medication alone, the moxibustion combined therapy significantly improved clinical symptoms in RA patients (P<0.05). Mechanistically, the moxibustion group demonstrated a simultaneous downregulation of key serum proinflammatory factors, including TNF-α and IL-17A, alongside a significant reduction in the bone resorption marker β-CTX. This therapeutic effect was linked to a suppression of abnormally activated Wnt pathway molecules. > Specifically, moxibustion significantly reduced serum levels of WNT3A, LRP-6, and β-catenin, while simultaneously upregulating the bone protective factor OPG and inhibiting GSK-3β (P < 0.05 for both intra- and intergroup comparisons). Furthermore, correlation analysis revealed positive associations between changes in β-catenin levels and those in TNF-α and WNT3A (P < 0.05), underscoring the pathway's central role in mediating the observed anti-inflammatory and bone-protective effects.