{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,30]],"date-time":"2026-08-30T17:15:02Z","timestamp":1788110102484,"version":"build-2803163510"},"reference-count":52,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,8,30]],"date-time":"2026-08-30T00:00:00Z","timestamp":1788048000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,30]],"date-time":"2026-08-30T00:00:00Z","timestamp":1788048000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82472525"],"award-info":[{"award-number":["82472525"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82272567"],"award-info":[{"award-number":["82272567"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82470272"],"award-info":[{"award-number":["82470272"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82502941"],"award-info":[{"award-number":["82502941"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Osteoporosis, characterized by imbalanced bone homeostasis, is driven by excessive osteoclast\u2010mediated bone resorption, yet the epitranscriptomic regulation via m\n                    <jats:sup>6<\/jats:sup>\n                    A modification remains unclear. Here, we identify WTAP, a component of the m\n                    <jats:sup>6<\/jats:sup>\n                    A methyltransferase complex, as a critical negative regulator of osteoclastogenesis. Myeloid\u2010specific Wtap knockout in mice exacerbates osteoclast formation and osteoporotic bone loss. Mechanistically, WTAP mediates m\n                    <jats:sup>6<\/jats:sup>\n                    A deposition on Csflr mRNA, promoting degradation via the key m\n                    <jats:sup>6<\/jats:sup>\n                    A reader YTHDF2 and downregulating CSF1R expression, thereby enhancing osteoclastogenesis and bone loss in estrogen\u2010deficient osteoporosis. We further discover that KLF9, induced during osteoclast differentiation, translocates to the nucleus to directly repress Wtap transcription, initiating this pathological process. Concurrent conditional knockout of KLF9 in osteoclast precursors rescues the exacerbated osteoporotic bone loss driven by myeloid\u2010specific Wtap deficiency in vivo. This KLF9\/WTAP\/YTHDF2\/m\n                    <jats:sup>6<\/jats:sup>\n                    A\/CSF1R axis establishes a novel epigenetic circuit regulating bone resorption. Therapeutically, targeting this axis via AAV\u2010mediated Wtap overexpression or pharmacological CSF1R inhibition with pexidartinib effectively ameliorates bone loss in osteoporotic mice. Our findings elucidate a previously unrecognized epitranscriptomic mechanism controlling osteoclastogenesis and highlight its therapeutic potential for pathological bone resorption.\n                  <\/jats:p>","DOI":"10.1002\/advs.77227","type":"journal-article","created":{"date-parts":[[2026,8,30]],"date-time":"2026-08-30T16:40:48Z","timestamp":1788108048000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["WTAP Transcriptional Suppression by KLF9 Drives Osteoclastogenesis via M\n                    <sup>6<\/sup>\n                    A\u2010Mediated Regulation of CSF1R Signaling in Estrogen\u2010Deficient Osteoporosis"],"prefix":"10.1002","author":[{"given":"Chen","family":"Shen","sequence":"first","affiliation":[{"name":"Department of Orthopedics The First Affiliated Hospital of Soochow University  Suzhou Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8681-5096","authenticated-orcid":false,"given":"Xin","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Orthopedics The First Affiliated Hospital of Soochow University  Suzhou Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaoran","family":"Ge","sequence":"additional","affiliation":[{"name":"Department of Orthopedics The First Affiliated Hospital of Soochow University  Suzhou Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Orthopedics The First Affiliated Hospital of Soochow University  Suzhou Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziyu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Orthopedics The First Affiliated Hospital of Soochow University  Suzhou Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chang","family":"Lv","sequence":"additional","affiliation":[{"name":"Department of Orthopedics The First Affiliated Hospital of Soochow University  Suzhou Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Orthopedics The First Affiliated Hospital of Soochow University  Suzhou Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenhao","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Orthopedics The First Affiliated Hospital of Soochow University  Suzhou Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Qin","sequence":"additional","affiliation":[{"name":"Department of Orthopedics The First Affiliated Hospital of Soochow University  Suzhou Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qifeng","family":"Sheng","sequence":"additional","affiliation":[{"name":"Department of Orthopedics The First Affiliated Hospital of Soochow University  Suzhou Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qihan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Orthopedics The First Affiliated Hospital of Soochow University  Suzhou Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1440-1345","authenticated-orcid":false,"given":"Hongxia","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Cardiology The First Affiliated Hospital of Soochow University  Suzhou Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Orthopedics The First Affiliated Hospital of Soochow University  Suzhou Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9459-7981","authenticated-orcid":false,"given":"Huilin","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Orthopedics The First Affiliated Hospital of Soochow University  Suzhou Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4375-2803","authenticated-orcid":false,"given":"Dechun","family":"Geng","sequence":"additional","affiliation":[{"name":"Department of Orthopedics The First Affiliated Hospital of Soochow University  Suzhou Jiangsu China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,30]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/jbmr\/zjae119"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(25)01385\u20106"},{"issue":"12","key":"e_1_2_11_4_1","doi-asserted-by":"crossref","first-page":"3318","DOI":"10.1172\/JCI27071","article-title":"Pathogenesis of Osteoporosis: Concepts, Conflicts, and Prospects","volume":"115","author":"Raisz L. G.","year":"2005","journal-title":"Journal of Clinical Investigation"},{"issue":"6937","key":"e_1_2_11_5_1","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1038\/nature01658","article-title":"Osteoclast Differentiation and Activation","volume":"423","author":"Boyle W. J.","year":"2003","journal-title":"Nature"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a021857"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41574\u2010024\u201000969\u2010x"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jot.2025.07.008"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2022.108174"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392\u2010020\u201000450\u2010x"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41420\u2010024\u201001925\u20104"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010025\u201056615\u20101"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2025.1603068"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24021403"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419\u2010023\u201006263\u20104"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419\u2010022\u201005268\u20109"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419\u2010023\u201005565\u2010x"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1093\/stcltm\/szad020"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21051660"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jot.2024.08.008"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00438\u2010024\u201002203\u20109"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2022.106566"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2025.157472"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2022.116615"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41580\u2010019\u20100168\u20105"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2025.04.003"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2021.110060"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2023.114661"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2023.115344"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2019.108916"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.2038"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41413\u2010024\u201000374\u20100"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygeno.2023.110696"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419\u2010021\u201003915\u20101"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2023.216598"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2024.111098"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1093\/jleuko\/qiae021"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41389\u2010025\u201000583\u20100"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/cr.2014.3"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12943\u2010020\u201001204\u20107"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2016.05.041"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.ads4750"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12964\u2010023\u201001148\u20107"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.125544"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010022\u201034209\u20105"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202401399"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2024.103194"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010023\u201042025\u20108"},{"key":"e_1_2_11_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2025.06.017"},{"key":"e_1_2_11_50_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010019\u201009712\u2010x"},{"key":"e_1_2_11_51_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2418023122"},{"key":"e_1_2_11_52_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11427\u2010023\u20102541\u2010x"},{"key":"e_1_2_11_53_1","doi-asserted-by":"publisher","DOI":"10.3791\/64698"}],"container-title":["Advanced Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.77227","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/advs.77227","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/advs.77227","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,30]],"date-time":"2026-08-30T16:40:50Z","timestamp":1788108050000},"score":1,"resource":{"primary":{"URL":"https:\/\/advanced.onlinelibrary.wiley.com\/doi\/10.1002\/advs.77227"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,30]]},"references-count":52,"alternative-id":["10.1002\/advs.77227"],"URL":"https:\/\/doi.org\/10.1002\/advs.77227","archive":["Portico"],"relation":{},"ISSN":["2198-3844","2198-3844"],"issn-type":[{"value":"2198-3844","type":"print"},{"value":"2198-3844","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,30]]},"assertion":[{"value":"2026-05-18","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-10","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-30","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e77227"}}