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Bone microarchitecture was assessed by micro\u2013computed tomography and osteoclast and osteoblast parameters by histomorphometry. Osteoclast resorptive activity was evaluated using dentine slice pit assays. Mechanisms regulating osteoclastogenesis were investigated by RNA sequencing, real\u2010time quantitative polymerase chain reaction, immunoprecipitation, and immunoblotting. Bone formation and injury\u2010induced repair were assessed by dynamic histomorphometry and drill\u2010hole defect model. Therapeutic potential was evaluated in ovariectomized wild\u2010type (WT) and \u03b2\u2010TrCP2KO mice.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      \u03b2\u2010TrCP2KO and \u03b2\u2010TrCP2\n                      <jats:sup>\u0394M<\/jats:sup>\n                      mice exhibited the increased bone mass and reduced osteoclast numbers compared to WT, but not \u03b2\u2010TrCP1KO, mice. The \u03b2\u2010TrCP2KO bone marrow\u2013derived myeloid cells were treated with RANKL. The activity and markers of osteoclast were decreased and of interferon\u2010\u03b2 (IFN\u03b2) was increased. Mechanistically, \u03b2\u2010TrCP2\u2013mediated IKK\u03b5 ubiquitination and degradation are a critical event for enhancing IFN\u03b2 expression via IRF3 by RANKL or lipopolysaccharide stimulation. \u03b2\u2010TrCP2KO mice showed increased osteoblast differentiation and bone formation through \u03b2\u2010catenin stabilization and up\u2010regulation of osteogenic genes. In post\u2013osteoporosis induction therapeutic ovariectomized model, \u03b2\u2010TrCP2KO mice were protected from bone loss through both decreased osteoclast formation and enhanced osteoblast activity.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\u03b2\u2010TrCP2 regulates osteoclast formation by modulating IKK\u03b5\u2013IRF3\u2013IFN\u03b2 and NF\u2010\u03baB signaling pathway and influences osteoblast activity by \u03b2\u2010catenin accumulation. This study suggests that \u03b2\u2010TrCP2 has potential as a novel therapeutic target for osteoporosis.<\/jats:p>\n                    <jats:p>\n                      <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                        <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/art70351-gra-0001-m.png\">\n                          <jats:alt-text>image<\/jats:alt-text>\n                        <\/jats:graphic>\n                      <\/jats:boxed-text>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/art.70351","type":"journal-article","created":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T13:35:01Z","timestamp":1790343301000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Dual Effects of \u03b2\u2010\n                    <scp>TrCP2<\/scp>\n                    Deletion in Bone Homeostasis: Suppression of Osteoclastogenesis and Enhancement of Osteoblast Activity"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2895-4995","authenticated-orcid":false,"given":"Woo Jung","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Biological Sciences Sookmyung Women's University  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sora","family":"Han","sequence":"additional","affiliation":[{"name":"Research Institute of Women's Health Sookmyung Women's University  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hye In","family":"Ka","sequence":"additional","affiliation":[{"name":"Department of Physiology Ajou University School of Medicine  Suwon Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sun Young","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences Sookmyung Women's University  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiwon","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences Sookmyung Women's University  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyunjeong","family":"Joo","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences Sookmyung Women's University  Seoul Republic of Korea"},{"name":"Department of Surgery Cedars Sinai Medical Center  Los Angeles California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sujung","family":"Soh","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences Sookmyung Women's University  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaeun","family":"Oh","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences Sookmyung Women's University  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyung Hyun","family":"Yoo","sequence":"additional","affiliation":[{"name":"Laboratory of Biomedical Genomics, Department of Biological Sciences Sookmyung Women's University  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seung Hyun","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Oral Microbiology and Immunology, and Dental Research Institute School of Dentistry, Seoul National University  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yeongkag","family":"Kwon","sequence":"additional","affiliation":[{"name":"Department of Oral Microbiology and Immunology, and Dental Research Institute School of Dentistry, Seoul National University  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Choogon","family":"Lee","sequence":"additional","affiliation":[{"name":"Program in Neuroscience, Department of Biomedical Sciences Florida State University College of Medicine  Tallahassee"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyung\u2010Hyun","family":"Park\u2010Min","sequence":"additional","affiliation":[{"name":"Arthritis and Tissue Degeneration Program David Z. 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