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Identification of factors promoting osteoblast differentiation may provide potential targets for osteoporosis therapy. Through integral analyses of multiple datasets, NIBAN2 is found to be tightly associated with bone formation and osteoporosis. Indeed, NIBAN2 promotes osteoblast differentiation, and conditional Niban2 knockout in osteoblasts caused bone loss and insufficient mineralization. Mechanistically, NIBAN2 interacts with the HNRNPU\u2010cored spliceosome complex and alters its components to regulate the alternative splicing of\n                    <jats:italic>RUNX2<\/jats:italic>\n                    , which ultimately cause an increase in functional\n                    <jats:italic>RUNX2<\/jats:italic>\n                    (nuclear localization sequence complete) but a decrease in dysfunctional\n                    <jats:italic>RUNX2<\/jats:italic>\n                    (exon 6 exclusive) to reinforce osteoblast differentiation. Most importantly, NIBAN2 expression level negatively correlates with\n                    <jats:italic>RUNX2<\/jats:italic>\n                    spliced isoforms and bone loss in osteoporosis patients. NIBAN2 overexpression rescues bone loss in ovariectomized mice. Thus, this research identifies NIBAN2\u2010regulated\n                    <jats:italic>RUNX2<\/jats:italic>\n                    alternative splicing as a potential mechanism of osteoblast differentiation that may present strategies for antagonizing osteoporosis.\n                  <\/jats:p>","DOI":"10.1002\/advs.202416536","type":"journal-article","created":{"date-parts":[[2025,3,11]],"date-time":"2025-03-11T23:46:04Z","timestamp":1741736764000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Identification of NIBAN2\u2010Regulated\n                    <i>RUNX2<\/i>\n                    Alternative Splicing Presents Novel Strategies for Antagonizing Osteoporosis"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1436-4265","authenticated-orcid":false,"given":"Sheng","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Spine Surgery and Musculoskeletal Tumor Zhongnan Hospital of Wuhan University  No. 163 Donghu Road Wuhan Hubei 430071 P. 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