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Bortezomib is novel antimyeloma agent that has a direct beneficial effect on bone formation. However, the role of bortezomib in osteoclastogenesis and underlying mechanisms remains to be fully comprehended. In the present study, we show that bortezomib directly inhibited the receptor activator of nuclear factor \u03baB ligand (RANKL)\u2013 and lipopolysaccharide-dependent osteoclast differentiation. Interestingly, the bortezomib-mediated inhibition of osteoclastogenesis was transient, since the removal of bortezomib from culture completely restored osteoclast differentiation. Bortezomib impeded the induction and nuclear localization of nuclear factor of activated T cells, cytoplasmic 1 and reduced both macrophage colony-stimulating factor\u2013 and RANKL-induced extracellular-signal-regulated kinase (ERK) phosphorylation. In a mouse model of periodontitis, bortezomib prevented alveolar bone erosion induced by Porphyromonas gingivalis lipopolysaccharide. These data not only suggest a previously unappreciated mechanism by which bortezomib regulates bone resorption but also propose novel applications of bortezomib beyond its use as an antimyeloma agent.<\/jats:p>","DOI":"10.1177\/0022034515592592","type":"journal-article","created":{"date-parts":[[2015,6,30]],"date-time":"2015-06-30T20:42:36Z","timestamp":1435696956000},"page":"1243-1250","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":19,"title":["Bortezomib Inhibits Osteoclastogenesis and\n                    <i>Porphyromonas gingivalis<\/i>\n                    Lipopolysaccharide-induced Alveolar Bone Resorption"],"prefix":"10.1177","volume":"94","author":[{"given":"Y.-G.","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Periodontology, School of Dentistry, Kyungpook National University, Daegu, 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