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However, the molecular mechanisms controlling this balance across skeletal homeostasis and disease remain unclear. Here, transcriptomic analysis of human osteoporotic bone samples revealed significant downregulation of Ift20 and Wwtr1 in osteoblast\u2010lineage cells. Using osteoblast\u2010specific knockout models, we found that loss of both Ift20 and Wwtr1 in the osteoblast lineage caused severe bone loss and excessive bone marrow adipose tissue accumulation, which was further aggravated under ovariectomy and high\u2010fat diet conditions. Mechanistically, Ift20 localized to primary cilia and interacted with transforming growth factor\u2010\u03b2 receptor II (T\u03b2RII), protecting it from c\u2010Cbl\u2010mediated ubiquitination and degradation to sustain TGF\u2010\u03b2 signaling. Meanwhile, Wwtr1 directly bound the\n                    <jats:italic>T\u03b2RII<\/jats:italic>\n                    promoter to promote its transcription. Loss of Ift20 and Wwtr1 converged on T\u03b2RII suppression, impairing osteoblast differentiation while enhancing adipogenesis and osteoclastogenesis. These findings reveal a previously unrecognized cilia\u2013transcription\u2013TGF\u2010\u03b2 regulatory mechanism that governs osteoblast\u2013adipocyte fate decisions and skeletal remodeling. The Ift20\u2013Wwtr1\u2013T\u03b2RII axis represents a critical safeguard of bone mass and marrow fat balance and may provide a therapeutic target for osteoporosis and metabolic bone diseases.\n                  <\/jats:p>","DOI":"10.1002\/mco2.70916","type":"journal-article","created":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T05:49:41Z","timestamp":1789969781000},"source":"Crossref","is-referenced-by-count":0,"title":["Ciliary Ift20 and Wwtr1 Coordinate Transforming Growth Factor\u2010\u03b2 Receptor II Signaling to Maintain Bone\u2013Fat Balance in Skeletal Homeostasis"],"prefix":"10.1002","volume":"7","author":[{"given":"Yang","family":"Li","sequence":"first","affiliation":[{"name":"Department of Basic and Translational Sciences School of Dental Medicine University of Pennsylvania  Philadelphia Pennsylvania USA"},{"name":"Department of Psychiatry and Behavioral Sciences School of Medicine Johns Hopkins University  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Basic and Translational Sciences School of Dental Medicine University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuting","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Basic and Translational Sciences School of Dental Medicine University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huijuan","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Behavioral Sciences School of Medicine Johns Hopkins University  Baltimore Maryland USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi\u2010Ping","family":"Li","sequence":"additional","affiliation":[{"name":"Division in Cellular and Molecular Medicine Department of Pathology and Laboratory Medicine Tulane University  New Orleans Louisiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7126-6901","authenticated-orcid":false,"given":"Shuying","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Basic and Translational Sciences School of Dental Medicine University of Pennsylvania  Philadelphia Pennsylvania USA"},{"name":"Center for Innovation &amp; Precision Dentistry School of Dental Medicine University of Pennsylvania  Philadelphia Pennsylvania USA"},{"name":"The Penn Center for Musculoskeletal Disorders School of Medicine University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,20]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00223-021-00885-6"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrgastro.2009.166"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1359\/jbmr.070813"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1011513223894"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2017.01.001"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2213-8587(14)70007-5"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41556-019-0437-8"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1615\/CritRevEukarGeneExpr.v19.i2.20"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.14336\/AD.2015.1206"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioactmat.2022.04.017"},{"key":"e_1_2_11_12_1","first-page":"668","article-title":"Current Advances in Regulation of Bone Homeostasis","volume":"2","author":"Al\u2010Bari A. 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