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The BM environment significantly influences the progression of MM. Celastrol, a natural compound derived from traditional Chinese medicine, exhibits significant anticancer effects. This study aimed to identify specific targets of celastrol and develop more effective and less toxic treatment options for MM. Celastrol is used as a probe to determine its specific target, pyridoxine\u20105\u2032\u2010phosphate oxidase (PNPO). Increased levels of PNPO are associated with poor outcomes in MM patients, and PNPO promotes MM cell proliferation and induces osteoclast differentiation through exosomes. Mechanistically, PNPO oxidizes disheveled 3\n                    <jats:sup>M282<\/jats:sup>\n                    (DVL3), leading to abnormal activation of the Wnt\/\u03b2\u2010catenin pathway. Based on the critical sites of PNPO\n                    <jats:sup>R95\/K117<\/jats:sup>\n                    , Eltrombopag is identified as a potential therapeutic candidate for MM. In addition, the experiments showed its efficacy in mouse models. Eltrombopag inhibited the growth of MM cells and reduced bone lesions by disrupting the interaction between PNPO and DVL3, as supported by preliminary clinical trials. The study highlights the importance of PNPO as a high\u2010risk gene in the development of MM and suggests that Eltrombopag may be a promising treatment option.\n                  <\/jats:p>","DOI":"10.1002\/advs.202407681","type":"journal-article","created":{"date-parts":[[2024,12,10]],"date-time":"2024-12-10T14:03:00Z","timestamp":1733839380000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["PNPO\u2010Mediated Oxidation of DVL3 Promotes Multiple Myeloma Malignancy and Osteoclastogenesis by Activating the Wnt\/\u03b2\u2010Catenin Pathway"],"prefix":"10.1002","volume":"12","author":[{"given":"Zhendong","family":"Deng","sequence":"first","affiliation":[{"name":"Nanjing Hospital of Chinese Medicine affiliated to Nanjing University of Chinese Medicine  Nanjing 210022 China"},{"name":"School of Medicine Nanjing University of Chinese Medicine  Nanjing 210023 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