{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T12:37:38Z","timestamp":1784810258784,"version":"3.55.0"},"reference-count":46,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"806","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Transl. Med."],"published-print":{"date-parts":[[2025,7,9]]},"abstract":"<jats:p>\n            Myeloma bone disease, a complication of multiple myeloma (MM), is characterized by impaired osteogenic function of bone marrow stromal cells (BMSCs) and can be an indicator of disease progression. The underlying mechanisms driving BMSC dysfunction are not yet fully understood. This work investigated MM cell interaction with BMSCs, finding that BMSC ciliogenesis is inhibited in the presence of myeloma cells. We demonstrated that direct interaction between myeloma cells and BMSCs through CD40-CD40L led to BMSC down-regulation of sentrin-specific protease 1 (SENP1), a cysteine protease that removes small ubiquitin-like modifier (SUMO) posttranslational modifications. SENP1 down-regulation led to increased SUMOylation of oral-facial-digital syndrome type 1 protein (OFD1), a centriole and centriolar satellite protein, at K931. Increased SUMOylation led to increased OFD1 protein stability and localization at centriolar satellites of primary cilia and decreased ciliogenesis. Consequently, BMSCs lacking primary cilia became desensitized to shear stress stimulation and decreased Hedgehog signaling activation. This cascade of events resulted in inhibited ciliogenesis and osteogenesis in myeloma-BMSC\u2013interacting models, in\n            <jats:italic>Prx1<\/jats:italic>\n            <jats:sup>Cre<\/jats:sup>\n            <jats:italic>Cd40l<\/jats:italic>\n            <jats:sup>f\/f<\/jats:sup>\n            mice, and in clinical samples. Treatment with an anti-CD40 neutralizing antibody effectively mitigated bone disruption and tumor burden in the Vk*MYC and SCID (severe combined immunodeficient)\u2013hu mouse models of MM. Overall, our study provides experimental insights into BMSC dysfunction in MM and suggests that targeting the CD40-SENP1-OFD1 axis could hold promise for MM treatment in clinical settings.\n          <\/jats:p>","DOI":"10.1126\/scitranslmed.adq2961","type":"journal-article","created":{"date-parts":[[2025,7,9]],"date-time":"2025-07-09T17:58:18Z","timestamp":1752083898000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":5,"title":["Myeloma interaction with bone marrow stromal cells suppresses ciliogenesis and osteogenic potential in myeloma bone disease"],"prefix":"10.1126","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1197-3222","authenticated-orcid":true,"given":"Ying","family":"Xie","sequence":"first","affiliation":[{"name":"Shandong Provincial Key Laboratory of Precision Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan 250117, Shandong, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2730-1562","authenticated-orcid":true,"given":"Zhaoyun","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Hematology, Tianjin Medical University General Hospital, Tianjin Key Laboratory of Bone Marrow Failure and Malignant Hemopoietic Clone Control, Tianjin Institute of Hematology, State Key Laboratory of Experimental Hematology, Tianjin 300052, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2183-1842","authenticated-orcid":true,"given":"Qian","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Hematology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin\u2019s Clinical Research Center for Cancer, Tianjin 300060, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-3926-978X","authenticated-orcid":true,"given":"Tiantian","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Experimental Hematology, Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Tianjin Medical University, Heping, Tianjin 300070, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5654-3317","authenticated-orcid":true,"given":"Jing","family":"Guo","sequence":"additional","affiliation":[{"name":"Shandong Provincial Key Laboratory of Precision Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan 250117, Shandong, 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