{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T21:02:36Z","timestamp":1790888556827,"version":"4.1.0"},"reference-count":41,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2020,3,17]],"date-time":"2020-03-17T00:00:00Z","timestamp":1584403200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81771491; 81871099; 81501052; 81701364; 81901426"],"award-info":[{"award-number":["81771491; 81871099; 81501052; 81701364; 81901426"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Cellular Molecular Medi"],"published-print":{"date-parts":[[2020,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Angelica sinensis (AS; Dang Gui), a traditional Chinese herb, has for centuries been used for the treatment of bone diseases, including osteoporosis and osteonecrosis. However, the effective ingredient and underlying mechanisms remain elusive. Here, we identified guaiacol as the active component of AS by two\u2010dimensional cell membrane chromatography\/C18 column\/time\u2010of\u2010flight mass spectrometry (2D CMC\/C18 column\/TOFMS). Guaiacol suppressed osteoclastogenesis and osteoclast function in bone marrow monocytes (BMMCs) and RAW264.7 cells in vitro in a dose\u2010dependent manner. Co\u2010immunoprecipitation indicated that guaiacol blocked RANK\u2010TRAF6 association and RANK\u2010C\u2010Src association. Moreover, guaiacol prevented phosphorylation of p65, p50, I\u03baB (NF\u2010\u03baB pathway), ERK, JNK, c\u2010fos, p38 (MAPK pathway) and Akt (AKT pathway), and reduced the expression levels of Cathepsin K, CTR, MMP\u20109 and TRAP. Guaiacol also suppressed the expression of nuclear factor of activated T\u2010cells cytoplasmic 1(NFATc1) and the RANKL\u2010induced Ca\n                    <jats:sup>2+<\/jats:sup>\n                    oscillation. In vivo, it ameliorated ovariectomy\u2010induced bone loss by suppressing excessive osteoclastogenesis. Taken together, our findings suggest that guaiacol inhibits RANKL\u2010induced osteoclastogenesis by blocking the interactions of RANK with TRAF6 and C\u2010Src, and by suppressing the NF\u2010\u03baB, MAPK and AKT signalling pathways. Therefore, this compound shows therapeutic potential for osteoclastogenesis\u2010related bone diseases, including postmenopausal osteoporosis.\n                  <\/jats:p>","DOI":"10.1111\/jcmm.15153","type":"journal-article","created":{"date-parts":[[2020,3,18]],"date-time":"2020-03-18T01:30:53Z","timestamp":1584495053000},"page":"5122-5134","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Guaiacol suppresses osteoclastogenesis by blocking interactions of RANK with TRAF6 and C\u2010Src and inhibiting NF\u2010\u03baB, MAPK and AKT pathways"],"prefix":"10.1111","volume":"24","author":[{"given":"Xin","family":"Zhi","sequence":"first","affiliation":[{"name":"Department of Orthopedics Trauma Shanghai Changhai Hospital Naval Military Medical University Shanghai China"},{"name":"Basic Medical School Naval Military Medical University Shanghai 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