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As a cancer of plasma cells, multiple myeloma (MM) is accompanied with rapid bone loss and fragility fracture. Bortezomib has been used as a first\u2010line for treating MM for decades. Recently, the potential protection of bortezomib on osteoporosis (OP) is reported; however, the specific mechanism involving bortezomib\u2010mediated antiosteoporotic effect is undetermined. In the present study, we assessed the effects of <jats:italic>in vitro<\/jats:italic> bortezomib treatment on osteogenesis and osteoclastogenesis and the protective effect on bone loss in ovariectomized (OVX) mice. Our results indicated that bortezomib treatment increased osteogenic differentiation of MC3T3\u2010E1 cells as evidenced by increased levels of matrix mineralization and osteoblast\u2010specific markers. In bortezomib\u2010treated bone marrow monocytes (BMMs), osteoclast differentiation was suppressed, substantiated by downregulated tartrate\u2010resistant acid phosphatase\u2010 (TRAP\u2010) positive multinucleated cells, areas of actin rings, pit formation, and osteoclast\u2010specific genes. Mechanistically, bortezomib exerted a protective effect against OP through the Smad ubiquitination regulatory factor\u2010 (SMURF\u2010) mediated ubiquitination pathway. Furthermore, <jats:italic>in vivo<\/jats:italic> intraperitoneal injection of bortezomib attenuated the bone microarchitecture in OVX mice. Accordingly, our findings corroborated that bortezomib might have future applications in the treatment of postmenopausal OP.<\/jats:p>","DOI":"10.1155\/2021\/9661200","type":"journal-article","created":{"date-parts":[[2021,12,31]],"date-time":"2021-12-31T20:20:56Z","timestamp":1640982056000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Bortezomib Rescues Ovariectomy\u2010Induced Bone Loss via SMURF\u2010Mediated Ubiquitination 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