{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T18:50:07Z","timestamp":1790275807841,"version":"4.1.0"},"reference-count":43,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2012,2,15]],"date-time":"2012-02-15T00:00:00Z","timestamp":1329264000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2012,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Receptor activator of NF-\u03baB ligand (RANKL) stimulation leads to the activation of mitogen-activated protein kinase (MAPK)\/AP-1 and Ca2+\u2013nuclear factor of activated T-cells cytoplasmic 1 (NFATc1) signaling pathways in osteoclastogenesis. Targeting these pathways has been an encouraging strategy for bone-related diseases, such as postmenopausal osteoporosis. In this study, we examined the effects of caffeic acid 3,4-dihydroxy-phenethyl ester (CADPE) on osteoclastogenesis. In mouse bone marrow monocytes (BMMs) and RAW264.7 cells, CADPE suppressed RANKL-induced osteoclast differentiation and actin-ring formation in a dose-dependent manner within non\u2013growth inhibitory concentrations at the early stage, while CADPE had no effect on macrophage colony-stimulating factor (M-CSF)-induced proliferation and differentiation. At the molecular level, CADPE inhibited RANKL-induced phosphorylation of MAPKs, including extracellular signal-regulated kinases 1\/2 (ERK1\/2), p38, and c-Jun N-terminal kinase (JNK), without significantly affecting the NF-\u03baB signaling pathway. CADPE abrogated RANKL-induced activator protein 1 (AP-1)\/FBJ murine osteosarcoma viral oncogene homolog (c-Fos) nuclear translocation and activation. Overexpression of c-Fos prevented the inhibition by CADPE of osteoclast differentiation. Furthermore, CADPE suppressed RANKL-induced the tumor necrosis factor receptor associated factor 6 (TRAF6) interaction with c-src tyrosine kinase (c-Src), blocked RANKL-induced the phosphorylation of protein kinase B (AKT), and inhibited RANKL-induced Ca2+ oscillation. As a result, CADPE decreased osteoclastogenesis-related marker gene expression, including NFATc1, TRAP, cathepsin K, and c-Src. To test the effects of CADPE on osteoclast activity in vivo, we showed that CADPE prevented ovariectomy-induced bone loss by inhibiting osteoclast activity. Together, our data demonstrate that CADPE suppresses osteoclastogenesis and bone loss through inhibiting RANKL-induced MAPKs and Ca2+-NFATc1 signaling pathways. CADPE is a novel agent in the treatment of osteoclast-related diseases, such as osteoporosis. \u00a9 2012 American Society for Bone and Mineral Research.<\/jats:p>","DOI":"10.1002\/jbmr.1576","type":"journal-article","created":{"date-parts":[[2012,2,15]],"date-time":"2012-02-15T20:56:21Z","timestamp":1329339381000},"page":"1298-1308","source":"Crossref","is-referenced-by-count":84,"title":["Caffeic acid 3,4-dihydroxy-phenethyl ester suppresses receptor activator of NF-\u03baB ligand\u2013induced osteoclastogenesis and prevents ovariectomy-induced bone loss through inhibition of mitogen-activated protein kinase\/activator protein 1 and Ca2+\u2013nuclear factor of activated T-cells cytoplasmic 1 signaling pathways"],"prefix":"10.1093","volume":"27","author":[{"given":"Xian","family":"Wu","sequence":"first","affiliation":[{"name":"Shanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, 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