{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T11:33:47Z","timestamp":1789990427374,"version":"4.0.1"},"reference-count":21,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,8,13]],"date-time":"2025-08-13T00:00:00Z","timestamp":1755043200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Drug Development Research"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease affecting synovial joints. <jats:italic>Jinwu Jiangu Capsules<\/jats:italic> (JJC) has been shown to be effective in treating RA. However, the primary active components and the underlying molecular mechanisms of JJC in RA treatment remain unclear. This study investigates how the monomers of JJC regulate the DKK1\/Wnt\u2010OPG signaling axis and autophagy in RA, both in vivo and in vitro. Evaluate the antiarthritis effects of JJC using a Type II collagen\u2010induced arthritis (CIA) rat model. Histopathological analysis is conducted using HE staining, while qPCR, Western blot, ELISA, and GFP\u2010LC3 are used to assess the DKK1\/Wnt\u2010OPG signaling pathway and autophagy status. Key components of the capsule are identified through network pharmacology. The effects of these components on osteoblasts are evaluated using CCK\u20108, alizarin red staining, ALP activity assay, EdU staining, MDC detection, and TRAP staining. JJC effectively reduced the expression of DKK1, RANKL, \u03b2\u2010catenin, and p\u2010\u03b2\u2010catenin, while increasing the levels of autophagy\u2010related proteins such as Beclin\u20101, LC3, and Atg5, thus positively affecting the progression of RA. Network pharmacology analysis revealed that ethyl linoleate (EL), a key component of JJC, targeted DKK1. RA model rats showed a dose\u2010dependent response to EL. It significantly reduced cell proliferation and inflammatory cell infiltration in knee joint synovium and improved tissue structure. EL lowered DKK1 and RANKL levels in knee joint synovium and bone tissue, and increased OPG and LC3 expression. Additionally, it enhanced ALP activity and survival of osteoblasts, promoted cell proliferation and autophagy, protected osteoblast function, and inhibited the differentiation of PBMCs into osteoclasts, demonstrating its potential therapeutic effects on RA pathology. EL, a key component of JJC, exhibits significant therapeutic potential and positive effects in the treatment of RA by influencing the DKK1\/Wnt\u2010OPG signaling axis and autophagic processes.<\/jats:p>","DOI":"10.1002\/ddr.70135","type":"journal-article","created":{"date-parts":[[2025,8,14]],"date-time":"2025-08-14T06:35:14Z","timestamp":1755153314000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Ethyl Linoleate Ameliorates Synovial Cell Proliferation and Inflammatory Cell Infiltration in Rheumatoid Arthritis Through DKK1\/Wnt\u2010OPG Signal Axis and Autophagy"],"prefix":"10.1002","volume":"86","author":[{"given":"Zong","family":"Jiang","sequence":"first","affiliation":[{"name":"Second Clinical Medical College Guizhou University of Traditional Chinese Medicine Guiyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"XiaoLing","family":"Yao","sequence":"additional","affiliation":[{"name":"Second Clinical Medical College Guizhou University of Traditional Chinese Medicine Guiyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Cai","sequence":"additional","affiliation":[{"name":"Second Clinical Medical College Guizhou University of Traditional Chinese Medicine Guiyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"WeiYa","family":"Lan","sequence":"additional","affiliation":[{"name":"Second Clinical Medical College Guizhou University of Traditional Chinese Medicine Guiyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7742-7171","authenticated-orcid":false,"given":"WuKai","family":"Ma","sequence":"additional","affiliation":[{"name":"Second Clinical Medical College Guizhou University of Traditional Chinese Medicine Guiyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-5492-4182","authenticated-orcid":false,"given":"XueMing","family":"Yao","sequence":"additional","affiliation":[{"name":"Second Clinical Medical College Guizhou University of Traditional Chinese Medicine Guiyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang","family":"Tang","sequence":"additional","affiliation":[{"name":"Second Clinical Medical College Guizhou University of Traditional Chinese Medicine Guiyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,8,13]]},"reference":[{"key":"e_1_2_12_2_1","first-page":"4","article-title":"Research Progress on the Treatment of Rheumatoid Arthritis With Miao Medicine Jinwujiangu Decoction","volume":"41","author":"Cai X.","year":"2021","journal-title":"Chinese Journal of Gerontology"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2014.07.018"},{"key":"e_1_2_12_4_1","first-page":"1213","article-title":"Linoleic Acid Ameliorates Inflammation in Rheumatoid Arthritis Rats via Regulation of TLR4\/NF\u2010\u03baB Signaling Pathway","volume":"37","author":"Hu D.","year":"2021","journal-title":"Chinese Pharmacological Bulletin"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1155\/2023\/4814412"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/jms.4711"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/1750-3841.12401"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcla.22595"},{"key":"e_1_2_12_9_1","first-page":"513","article-title":"Effects of Jinwu Jiangu Capsule on Proliferation, Migration and Apoptosis of RA\u2010FLS Cells China","volume":"37","author":"Ling Y.","year":"2022","journal-title":"Journal of Traditlonal Chinese Medicine and Pharmacy"},{"key":"e_1_2_12_10_1","first-page":"8","article-title":"Ethyl Linoleate Inhibits Inflammatory Reaction Induced by Titanium Particles and Its Mechanism Chinese","volume":"20","author":"Liu G.","year":"2016","journal-title":"Journal of Tissue Engineering Research"},{"key":"e_1_2_12_11_1","first-page":"585","article-title":"[Effects of Jinwu Jiangu Recipe on IL\u201017\/STAT3 Signals in Rheumatoid Arthritis Synoviocytes]","volume":"43","author":"Ma W. K.","year":"2018","journal-title":"Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(17)31472-1"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(12)62192-8"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2014.01.017"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms17010029"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2024.119099"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/bmc.5389"},{"key":"e_1_2_12_18_1","first-page":"607","article-title":"Clinical Observation on Jinwu Jiangu Capsules Combined With Leflunomide in Treatment for 38 Cases of \uff32heumatoid Arthritis of Cold\u2010Dampness Obstruction Type","volume":"61","author":"Xu H.","year":"2020","journal-title":"Journal of Traditional Chinese Medicine"},{"key":"e_1_2_12_19_1","first-page":"5","article-title":"Pharmacological Toxicology Research of Miao Medicine Jinwu Jiangu Capsule","volume":"42","author":"Xu H.","year":"2020","journal-title":"Journal of Guizhou University of Traditional Chinese Medicine"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2022.154268"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2022.926901"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.19604\/j.cnki.dys.2018.z1.052"}],"container-title":["Drug Development Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ddr.70135","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T21:10:49Z","timestamp":1760389849000},"score":1,"resource":{"primary":{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/10.1002\/ddr.70135"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,13]]},"references-count":21,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2025,9]]}},"alternative-id":["10.1002\/ddr.70135"],"URL":"https:\/\/doi.org\/10.1002\/ddr.70135","archive":["Portico"],"relation":{},"ISSN":["0272-4391","1098-2299"],"issn-type":[{"value":"0272-4391","type":"print"},{"value":"1098-2299","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,13]]},"assertion":[{"value":"2025-02-24","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-07-24","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-08-13","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70135"}}