{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T16:04:04Z","timestamp":1784131444489,"version":"3.55.0"},"reference-count":41,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T00:00:00Z","timestamp":1779408000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"\n Background and aims<\/jats:title>\n The pathological core of rheumatoid arthritis (RA) is progressive bone destruction driven by chronic inflammation. The Wnt\/\u03b2-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\/\u03b2-catenin signaling pathway to coordinate inflammation and bone metabolism in rheumatoid arthritis (RA).<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n 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-\u03b1), 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-3\u03b2), \u03b2-catenin, osteoprotegerin (OPG), and beta-C-terminal telopeptide of type I collagen (\u03b2-CTX) were measured.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Compared with the conventional control group alone, moxibustion combined therapy significantly improved clinical symptoms in RA patients (P&lt;0.05). Mechanistically, the moxibustion group simultaneously downregulated serum proinflammatory factors (TNF-\u03b1, IL-17A) and bone resorption marker \u03b2-CTX, suppressed abnormally activated Wnt pathway molecules (WNT3A, LRP-6, \u03b2-catenin), and upregulated the bone protective factor OPG while inhibiting GSK-3\u03b2 (P &lt; 0.05 for both intra- and intergroup comparisons). Correlation analysis revealed positive correlations between \u03b2-catenin changes and those in TNF-\u03b1 and WNT3A (\n P<\/jats:italic>\n &lt;\u00a00.05).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n 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-\u03b1 and IL-17A, thereby activating and regulating the Wnt\/\u03b2-catenin signaling pathway. This modulates serum levels of OPG and \u03b2-CTX, leading to systemic improvement in bone metabolic balance and exerting a multi-target therapeutic effect.<\/jats:p>\n <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1808931","type":"journal-article","created":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T04:33:59Z","timestamp":1779424439000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Mechanistic study on the reduction of TNF-\u03b1 and \u03b2-CTX levels in RA patients by moxibustion combined with western medication through regulation of the Wnt\/\u03b2-catenin pathway"],"prefix":"10.3389","volume":"17","author":[{"given":"Hui","family":"Wang","sequence":"first","affiliation":[{"name":"College of Acupuncture and Tuina, Chengdu University of Traditional Chinese Medicine","place":["Chengdu, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heshan","family":"Chen","sequence":"additional","affiliation":[{"name":"College of Acupuncture and Tuina, Chengdu University of Traditional Chinese Medicine","place":["Chengdu, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, Chengdu University of Traditional Chinese Medicine Affiliated Hospital","place":["Chengdu, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Yang","sequence":"additional","affiliation":[{"name":"College of Acupuncture and Tuina, Chengdu University of Traditional Chinese Medicine","place":["Chengdu, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaojuan","family":"Hong","sequence":"additional","affiliation":[{"name":"College of Acupuncture and Tuina, Chengdu University of Traditional Chinese Medicine","place":["Chengdu, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Wu","sequence":"additional","affiliation":[{"name":"College of Acupuncture and Tuina, Chengdu University of Traditional Chinese Medicine","place":["Chengdu, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,22]]},"reference":[{"key":"B1","first-page":"194","article-title":"Effect of moxibustion at \"Zusanli\"(ST36) and \"Shenshu\"(BL23) on miR-155-mediated TLR4\/NF-\u03baB signaling involving amelioration of synovitis in rheumatoid arthritis rats","volume":"46","author":"Zhu","year":"2021","journal-title":"Zhen Ci Yan Jiu"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2022.155835","article-title":"Moxibustion regulates the polarization of macrophages through the IL-4\/STAT6 pathway in rheumatoid arthritis","volume":"152","author":"Zhong","year":"2022","journal-title":"Cytokine"},{"key":"B3","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1089\/rej.2024.0052","article-title":"Moxibustion regulates the expression of T cells in rheumatoid arthritis through Tim-3\/Gal-9 signaling pathway","volume":"28","author":"Zhong","year":"2025","journal-title":"Rejuvenation Res"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1155\/2021\/6658946","article-title":"The effects of moxibustion on PD-1\/PD-L1-related molecular expression and inflammatory cytokine levels in RA rats","volume":"2021","author":"Zhong","year":"2021","journal-title":"Evid Based Complement Alternat Med"},{"key":"B5","article-title":"Effect of different suspension moxibustion methods on syndrome characteristics of rats with rheumatoid arthritis of heat bi syndrome based on \"moxibustion can be used for heat syndrome","volume":"43","author":"Zhao","year":"2023","journal-title":"Zhongguo Zhen Jiu"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/j.joim.2022.06.002","article-title":"Moxibustion regulates T-regulatory\/T-helper 17 cell balance by modulating the microRNA-221\/suppressor of cytokine signaling 3 axis in a mouse model of rheumatoid arthritis","volume":"20","author":"Zhao","year":"2022","journal-title":"J Integr Med"},{"key":"B7","article-title":"Clinical effect and mechanism of moxibustion combined with western medication for rheumatoid arthritis of liver-kidney deficiency","volume":"41","author":"Zhang","year":"2021","journal-title":"Zhongguo Zhen Jiu"},{"key":"B8","article-title":"Moxibustion of Zusanli (ST36) and Shenshu (BL23) alleviates the inflammation of rheumatoid arthritis in rats through regulating macrophage migration inhibitory factor\/glucocorticoids signaling","volume":"44","author":"Linlin","year":"2024","journal-title":"J Tradit Chin Med"},{"key":"B9","article-title":"Effect of moxibustion on the expressions of hypoxia inducible factor-1\u03b1 and vascular endothelial growth factor in ankle synovial tissue of rats with adjuvant arthritis","volume":"48","author":"Zhang","year":"2023","journal-title":"Zhen Ci Yan Jiu"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1002\/art.27584","article-title":"Rheumatoid arthritis classification criteria: An American College of Rheumatology\/European League Against Rheumatism collaborative initiative","volume":"62","author":"Aletaha","year":"2010","journal-title":"Arthritis Rheumatism"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.55563\/clinexprheumatol\/mf9dxk","article-title":"DAS28(3)CRP is a reliable measure of disease activity in pregnant women with rheumatoid arthritis","volume":"41","author":"Raine","year":"2023","journal-title":"Clin Exp Rheumatol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1097\/md.0000000000030701","article-title":"Effect of chrono-moxibustion and its influence on circadian rhythm for rheumatoid arthritis: A study protocol for a randomized controlled trial","volume":"101","author":"Yu","year":"2022","journal-title":"Med (Baltimore)"},{"key":"B13","article-title":"Design of a control system for moxibustion robotic arm for dynamic three-dimensional surface tracking [master's thesis]","author":"Zhu","year":"2024"},{"key":"B14","article-title":"Regulatory effect of moxibustion on LTB4\/MMP-9 in serum of patients with rheumatoid arthritis","volume":"48","author":"Tang","year":"2023","journal-title":"Zhen Ci Yan Jiu"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1155\/2021\/6637554","article-title":"Effect of moxibustion on \u03b2-EP and Dyn levels of pain-related indicators in patients with rheumatoid arthritis","volume":"2021","author":"Wang","year":"2021","journal-title":"Evid Based Complement Alternat Med"},{"key":"B16","article-title":"Study on the anti-inflammatory mechanism of moxibustion in rheumatoid arthritis in rats based on phospholipaseA2 signaling inhibition by Annexin 1","volume":"44","author":"Yanding","year":"2024","journal-title":"J Tradit Chin Med"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1007\/s11655-025-4232-z","article-title":"New paradigm for rheumatoid arthritis treatment: a review of 'crosstalk' mechanism of multi-targeted intervention on cytokine\/chemokine networks by Chinese medicine","volume":"32","author":"Yan","year":"2026","journal-title":"Chin J Integr Med"},{"key":"B18","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1186\/s41065-022-00221-4","article-title":"Transcriptome sequencing reveals core regulation modules and gene signatures of Zusanli acupoints in response to different moxibustion warm stimulation in adjuvant arthritis rat","volume":"159","author":"Zeng","year":"2022","journal-title":"Hereditas"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1007\/s11726-024-1445-1","article-title":"Effects of pecking moxibustion on pattern characteristics and synovial cell ultrastructure of rats with rheumatoid arthritis due to damp heat affecting bones\/joints","volume":"22","author":"Yue","year":"2024","journal-title":"J Acupuncture Tuina Sci"},{"key":"B20","article-title":"Effect of moxibustion on JAK2\/STAT3 signal pathway in synovial tissues of rabbits with adjuvant arthritis under the overexpression of NLRP3 inflammatory bodies","volume":"47","author":"Xi","year":"2022","journal-title":"Zhen Ci Yan Jiu"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1016\/j.dcmed.2025.05.010","article-title":"Integrated plasma and synovial membrane lipidomic profiling revealing the therapeutic effects of moxibustion in collagen-induced arthritis rat models","volume":"8","author":"Wen","year":"2025"},{"key":"B22","doi-asserted-by":"publisher","first-page":"243","DOI":"10.1186\/s13075-023-03224-2","article-title":"Wilforine inhibits rheumatoid arthritis pathology through the Wnt11\/\u03b2-catenin signaling pathway axis","volume":"25","author":"Huang","year":"2023","journal-title":"Arthritis Res Ther"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1089\/rej.2024.0110","article-title":"Moxibustion's impact on ferroptosis regulation: a key to relieving inflammatory injury in rheumatoid arthritis","volume":"28","author":"Wang","year":"2025","journal-title":"Rejuvenation Res"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.3390\/jcm10132905","article-title":"Bone metabolism and RANKL\/OPG ratio in rheumatoid arthritis women treated with TNF-\u03b1 inhibitors","volume":"10","author":"Jura-P\u00f3\u0142torak","year":"2021","journal-title":"J Clin Med"},{"key":"B25","first-page":"96","article-title":"Mechanisms of electroacupuncture at foot shaoyang meridian acupoints on inflammatory response in postmenopausal osteoporosis rats based on the PI3K\/AKT signaling pathway","volume":"51","author":"L\u00fc","year":"2026","journal-title":"Zhen Ci Yan Jiu"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.829409","article-title":"Comparison of efficacy of acupuncture-related therapy in the treatment of rheumatoid arthritis: a network meta-analysis of randomized controlled trials","volume":"13","author":"Wan","year":"2022","journal-title":"Front Immunol"},{"key":"B27","first-page":"993","article-title":"Comparison of the effect of moxibustion at \"Zusanli\" (ST36) on the polarization of synovial macrophages of knee joints in rats with knee osteoarthritis and rheumatoid arthritis","volume":"48","author":"Wang","year":"2023","journal-title":"Zhen Ci Yan Jiu"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2024.112953","article-title":"A synergistic effect of triptolide and curcumin on rheumatoid arthritis by improving cell proliferation and inducing cell apoptosis via inhibition of the IL-17\/NF-\u03baB signaling pathway","volume":"142","author":"Zhang","year":"2024","journal-title":"Int Immunopharmacol"},{"key":"B29","article-title":"Moxibustion as an adjunctive treatment for rheumatoid arthritis and its effects on the serum levels of SOST and \u03b2-catenin","volume":"43","author":"Tao","year":"2023","journal-title":"Zhongguo Zhen Jiu"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2025.157479","article-title":"Metabolomics and network pharmacology revealing the transdermal moxibustion compounds and their therapeutic mechanisms for rheumatoid arthritis","volume":"148","author":"Lai","year":"2025","journal-title":"Phytomedicine"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.3969\/j.issn.1003-0034.2020.01.018","article-title":"Research progress on mechanism of acupuncture and moxibustion promoting fracture healing","volume":"33","author":"Chen","year":"2020","journal-title":"Zhongguo Gu Shang"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.12182\/20250960106","article-title":"Cheng's Juanbi Decoction inhibits rheumatoid arthritis pathology by blocking the WTAP-Wnt7b-Wnt\/\u03b2-catenin signaling axis","volume":"56","author":"Wu","year":"2026","journal-title":"J Sichuan Univ (Med Sci)"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2022.109328","article-title":"Acid sensor ASIC1a induces synovial fibroblast proliferation via Wnt\/\u03b2-catenin\/c-Myc pathway in rheumatoid arthritis","volume":"113","author":"Xu","year":"2022","journal-title":"Int Immunopharmacol"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2023.155064","article-title":"Wnt\/\u03b2-catenin signaling pathway promotes abnormal activation of fibroblast-like synoviocytes and angiogenesis in rheumatoid arthritis and the intervention of Er Miao San","volume":"120","author":"Chen","year":"2023","journal-title":"Phytomedicine"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.12182\/20250160604","article-title":"Moxibustion inhibits postmenopausal bone loss by regulating the metabolism of gut microbiota-related serotonin","volume":"56","author":"Huang","year":"2025","journal-title":"Sichuan Da Xue Xue Bao Yi Xue Ban"},{"key":"B36","article-title":"Research progression of acupuncture-moxibustion in treatment of rheumatoid arthritis","volume":"44","author":"Lin","year":"2024","journal-title":"Zhongguo Zhen Jiu"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000036875","article-title":"Immunological studies on acupuncture and moxibustion treatment of rheumatoid arthritis: a review","volume":"103","author":"Sun","year":"2024","journal-title":"Medicine"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.3906\/sag-2102-367","article-title":"Wnt signaling pathway activities may be altered in primary Sjogren's syndrome","volume":"51","author":"Karata\u015f","year":"2021","journal-title":"Turk J Med Sci"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1007\/s10067-017-3689-3","article-title":"Glucocorticoid therapy causes contradictory changes of serum Wnt signaling-related molecules in systemic autoimmune diseases","volume":"37","author":"Kawazoe","year":"2018","journal-title":"Clin Rheumatol"},{"key":"B40","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1016\/j.jdermsci.2019.08.007","article-title":"TNF-\u03b1 and IL-17A induce the expression of lympho-epithelial Kazal-type inhibitor in epidermal keratinocytes","volume":"96","author":"Sugihara","year":"2019","journal-title":"J Dermatol Sci"},{"key":"B41","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1007\/s11906-022-01211-7","article-title":"Arterial stiffness and the canonical WNT\/\u03b2-catenin pathway","volume":"24","author":"Vall\u00e9e","year":"2022","journal-title":"Curr Hypertens Rep"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1808931\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T15:09:26Z","timestamp":1784128166000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2026.1808931\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,22]]},"references-count":41,"alternative-id":["10.3389\/fimmu.2026.1808931"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2026.1808931","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,22]]},"article-number":"1808931"}}