{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T14:50:11Z","timestamp":1789829411145,"version":"4.0.1"},"reference-count":41,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2022,8,6]],"date-time":"2022-08-06T00:00:00Z","timestamp":1659744000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81330043"],"award-info":[{"award-number":["81330043"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal Orthopaedic Research"],"published-print":{"date-parts":[[2023,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Osteoarthritis (OA) is a chronic degenerative bone and joint disease common in middle\u2010aged and elderly people. Currently, there is no satisfactory pharmacological treatment. Eugenol is a phenolic compound that has been shown to exert biological anti\u2010inflammatory, antioxidant, and antiapoptotic effects in multiple systems and organs of the human body. However, its therapeutic effect on OA is unclear. This study examined the effect of eugenol on OA using an anterior cruciate ligament transection (ACLT) model in mice and its related signaling pathways in interleukin\u20101\u03b2 (IL\u20101\u03b2)\u2010stimulated human chondrocytes. A certain concentration of eugenol inhibited the decrease in cell viability induced by IL\u20101\u03b2 or carbonyl cyanide 3\u2010chlorophenylhydrazone (CCCP). In vitro, eugenol effectively inhibited CCCP\u2010induced chondrocyte apoptosis and mitochondrial membrane potential changes and inhibited the expressions of ADAMTS4 and MMP13 upregulated by IL\u20101\u03b2. In vivo, ACLT induced destruction of the articular cartilage and subchondral bone of the mouse tibial plateau, while eugenol effectively protected the cartilage and subchondral bone from such damage. At the same time, eugenol reduced the ACLT\u2010induced upregulation of ADAMTS4 and MMP13 and the downregulation of type II collagen (COLII) and aggrecan in the mouse knee cartilage. Eugenol also inhibited the increased expression of cartilage metabolism signaling molecules such as C\u2010telopeptides of COLII (CTX\u2010II) in ACLT\u2010induced mouse serum. Consistent with the specific changes in the messenger RNA chip, eugenol inhibited the phosphorylation of JAK3 and STAT4 induced by IL\u20101\u03b2. Together, these results suggest eugenol as an effective new drug for the prevention and treatment of OA.<\/jats:p>","DOI":"10.1002\/jor.25420","type":"journal-article","created":{"date-parts":[[2022,7,26]],"date-time":"2022-07-26T03:18:07Z","timestamp":1658805487000},"page":"747-758","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Eugenol protects chondrocytes and articular cartilage by downregulating the JAK3\/STAT4 signaling pathway"],"prefix":"10.1002","volume":"41","author":[{"given":"Zhimin","family":"Wu","sequence":"first","affiliation":[{"name":"Beijing Laboratory of Biomedical Materials Institute of Traumatology and Orthopaedics, Beijing Jishuitan Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Wang","sequence":"additional","affiliation":[{"name":"Beijing Laboratory of Biomedical Materials Institute of Traumatology and Orthopaedics, Beijing Jishuitan Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoqiang","family":"Yan","sequence":"additional","affiliation":[{"name":"Beijing Laboratory of Biomedical Materials Institute of Traumatology and Orthopaedics, Beijing Jishuitan Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6366-4758","authenticated-orcid":false,"given":"Chengai","family":"Wu","sequence":"additional","affiliation":[{"name":"Beijing Laboratory of Biomedical Materials Institute of Traumatology and Orthopaedics, Beijing Jishuitan Hospital  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,8,6]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2020.01.002"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2019.02.036"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(14)60802-3"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcna.2019.10.007"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21072358"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/cpr.13134"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41584-020-00533-7"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.matbio.2018.05.008"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells8111305"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.matbio.2022.04.006"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioactmat.2021.05.029"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12964-019-0411-x"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-319-41342-6_3"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.3109\/13880209.2014.950674"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13197-014-1573-6"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1155\/2018\/3957262"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/ptr.3725"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2021.678810"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/jor.23079"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2005.07.014"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12864-020-07228-z"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2019.02.037"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2020.101249"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-18208-y"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.247353"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.66532"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13075-020-02156-5"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2019.109733"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20246156"},{"issue":"8","key":"e_1_2_9_31_1","first-page":"963","article-title":"Effect of icariin on serum bone turnover markers expressions and histology changes in mouse osteoarthritis model","volume":"31","author":"Gao K","year":"2017","journal-title":"Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi"},{"issue":"4","key":"e_1_2_9_32_1","first-page":"3464","article-title":"Eugenol protects the transplanted heart against ischemia\/reperfusion injury in rats by inhibiting the inflammatory response and apoptosis","volume":"16","author":"Feng W","year":"2018","journal-title":"Exp Ther Med"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.3109\/00498259009047156"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1097\/00003086-198607000-00025"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1002\/jor.20178"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bjorl.2018.07.007"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1111\/and.13353"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1186\/ar1197"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.177.11.7880"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms18030484"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1080\/21655979.2021.2018976"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2018.07.024"}],"container-title":["Journal of Orthopaedic Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jor.25420","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jor.25420","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jor.25420","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,22]],"date-time":"2023-08-22T14:35:14Z","timestamp":1692714914000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jor.25420"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,8,6]]},"references-count":41,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2023,4]]}},"alternative-id":["10.1002\/jor.25420"],"URL":"https:\/\/doi.org\/10.1002\/jor.25420","archive":["Portico"],"relation":{},"ISSN":["0736-0266","1554-527X"],"issn-type":[{"value":"0736-0266","type":"print"},{"value":"1554-527X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,8,6]]},"assertion":[{"value":"2022-04-27","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-07-23","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-08-06","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}