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We recently identified that osteoclastogenic stimulator selenoprotein W (SELENOW) is upregulated via ERK signaling and downregulated via p38 signaling during receptor activator of nuclear factor (NF)-\u03ba\u0392 ligand (RANKL)-induced osteoclast differentiation. In the intrinsic physiological process, RANKL-induced downregulation of SELENOW maintains proper osteoclast differentiation; in contrast, forced overexpression of SELENOW leads to overactive osteoclast formation and function.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods and results<\/jats:title>\n            <jats:p>We observed that SELENOW is highly expressed in multiple myeloma-derived peripheral blood mononuclear cells (PBMCs) and mature osteoclasts when compared to healthy controls. Also, the level of tumor necrosis factor alpha (TNF\u03b1), a pathological osteoclastogenic factor, is increased in the PBMCs and serum of patients with multiple myeloma. ERK activation by TNF\u03b1 was more marked and sustained than that by RANKL, allowing SELENOW upregulation. Excessive expression of SELENOW in osteoclast progenitors and mature osteoclasts derived from multiple myeloma facilitated efficient nuclear translocation of osteoclastogenic transcription factors NF-\u03baB and NFATc1, which are favorable for osteoclast formation.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion<\/jats:title>\n            <jats:p>Our findings suggest a possibility that feedforward signaling of osteoclastogenic SELENOW by TNF\u03b1 derived from multiple myeloma induces overactive osteoclast differentiation, leading to bone loss during multiple myeloma.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1007\/s11033-024-09517-2","type":"journal-article","created":{"date-parts":[[2024,4,29]],"date-time":"2024-04-29T09:02:20Z","timestamp":1714381340000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Selenoprotein W engages in overactive osteoclast differentiation in multiple myeloma"],"prefix":"10.1007","volume":"51","author":[{"given":"Hyunsoo","family":"Kim","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiin","family":"Oh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min Kyoung","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyung Hee","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daewon","family":"Jeong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,4,29]]},"reference":[{"key":"9517_CR1","doi-asserted-by":"publisher","unstructured":"Feng X, McDonald JM (2011) Disorders of bone remodeling. 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