{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T15:46:01Z","timestamp":1780587961376,"version":"3.54.1"},"reference-count":38,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2017,1,19]],"date-time":"2017-01-19T00:00:00Z","timestamp":1484784000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Australian Health and Medical Research Council","award":["APP1107828"],"award-info":[{"award-number":["APP1107828"]}]},{"name":"Australian Health and Medical Research Council","award":["APP1127396"],"award-info":[{"award-number":["APP1127396"]}]},{"name":"Australian Health and Medical Research Council","award":["APP1127156"],"award-info":[{"award-number":["APP1127156"]}]},{"DOI":"10.13039\/100008158","name":"Arthritis Foundation of Australia","doi-asserted-by":"publisher","award":["The H J &G J Mckenzie grant"],"award-info":[{"award-number":["The H J &G J Mckenzie grant"]}],"id":[{"id":"10.13039\/100008158","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Western Australia Medical &amp; Health Research Infrastructure Fund"},{"name":"University of Western Australia Research Collaboration Awards"},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81473697"],"award-info":[{"award-number":["81473697"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"YangFan Innovative And Entrepreneurial Research Team Project","award":["2014YT02S008"],"award-info":[{"award-number":["2014YT02S008"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Pathological osteolysis is commonly associated with osteoporosis, bone tumors, osteonecrosis, and chronic inflammation. It involves excessive resorption of bone matrix by activated osteoclasts. Suppressing receptor activator of NF-\u03baB ligand (RANKL) signaling pathways has been proposed to be a good target for inhibiting osteoclast differentiation and bone resorption. Bajijiasu\u2014a natural compound derived from Morinda officinalis F. C. How\u2014has previously been shown to have anti-oxidative stress property; however, its effect and molecular mechanism of action on osteoclastogenesis and bone resorption remains unclear. In the present study, we found that Bajijiasu dose-dependently inhibited RANKL-induced osteoclast formation and bone resorption from 0.1 mM, and reached half maximal inhibitory effects (IC50) at 0.4 mM without toxicity. Expression of RANKL-induced osteoclast specific marker genes including cathepsin K (Ctsk), nuclear factor of activated T-cells cytoplasmic 1 (NFATc1), tartrate resistant acid phosphatase (TRAcP), vacuolar-type H+-ATPase V0 subunit D2 (V-ATPase d2), and (matrix metalloproteinase-2 (MMP2) was inhibited by Bajijiasu treatment. Luciferase reporter gene studies showed that Bajijiasu could significantly reduce the expression and transcriptional activity of NFAT as well as RANKL-induced NF-\u03baB activation in a dose-dependent manner. Further, Bajijiasu was found to decrease the RANKL-induced phosphorylation of extracellular signal-regulated kinases (ERK), inhibitor of \u03baB-\u03b1 (I\u03baB-\u03b1), NFAT, and V-ATPase d2. Taken together, this study revealed Bajijiasu could attenuate osteoclast formation and bone resorption by mediating RANKL signaling pathways, indicative of a potential effect of Bajijiasu on osteolytic bone diseases.<\/jats:p>","DOI":"10.3390\/ijms18010203","type":"journal-article","created":{"date-parts":[[2017,1,19]],"date-time":"2017-01-19T10:55:40Z","timestamp":1484823340000},"page":"203","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Bajijiasu Abrogates Osteoclast Differentiation via the Suppression of RANKL Signaling Pathways through NF-\u03baB and NFAT"],"prefix":"10.3390","volume":"18","author":[{"given":"Guoju","family":"Hong","sequence":"first","affiliation":[{"name":"The National Key Discipline and the Orthopedic Laboratory, Guangzhou University of Chinese Medicine, Guangzhou 510006, China"},{"name":"School of Pathology and Laboratory Medicine, The University of Western Australia, Nedlands WA 6009, Australia"},{"name":"Orthopedic Department, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Zhou","sequence":"additional","affiliation":[{"name":"School of Pathology and Laboratory Medicine, The University of Western Australia, Nedlands WA 6009, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuguang","family":"Shi","sequence":"additional","affiliation":[{"name":"College of Chinese Materia Medical, Guangzhou University of Chinese Medicine, Guangzhou 510006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"He","sequence":"additional","affiliation":[{"name":"The National Key Discipline and the Orthopedic Laboratory, Guangzhou University of Chinese Medicine, Guangzhou 510006, China"},{"name":"Orthopedic Department, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haibin","family":"Wang","sequence":"additional","affiliation":[{"name":"The National Key Discipline and the Orthopedic Laboratory, Guangzhou University of Chinese Medicine, Guangzhou 510006, China"},{"name":"Orthopedic Department, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiushi","family":"Wei","sequence":"additional","affiliation":[{"name":"The National Key Discipline and the Orthopedic Laboratory, Guangzhou University of Chinese Medicine, Guangzhou 510006, China"},{"name":"Orthopedic Department, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Chen","sequence":"additional","affiliation":[{"name":"The National Key Discipline and the Orthopedic Laboratory, Guangzhou University of Chinese Medicine, Guangzhou 510006, China"},{"name":"Orthopedic Department, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Longkai","family":"Qi","sequence":"additional","affiliation":[{"name":"College of Chinese Materia Medical, Guangzhou University of Chinese Medicine, Guangzhou 510006, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Tickner","sequence":"additional","affiliation":[{"name":"School of Pathology and Laboratory Medicine, The University of Western Australia, Nedlands WA 6009, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Lin","sequence":"additional","affiliation":[{"name":"College of Chinese Materia Medical, Guangzhou University of Chinese Medicine, Guangzhou 510006, China"},{"name":"Artepharm, Co., Ltd., Guangzhou 510000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiake","family":"Xu","sequence":"additional","affiliation":[{"name":"The National Key Discipline and the Orthopedic Laboratory, Guangzhou University of Chinese Medicine, Guangzhou 510006, China"},{"name":"School of Pathology and Laboratory Medicine, The University of Western Australia, Nedlands WA 6009, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2017,1,19]]},"reference":[{"key":"ref_1","first-page":"161","article-title":"The origin of osteoclasts","volume":"18","author":"Kurihara","year":"1990","journal-title":"Bull. 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