{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T14:28:50Z","timestamp":1786544930049,"version":"build-2736575974"},"reference-count":44,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["iubmb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["IUBMB Life"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>DNA N6\u2010methyladenine (6\u2009mA) has recently been recognized as a novel epigenetic modification, with ALKBH4 identified as a specific demethylase. However, the role of ALKBH4 and DNA 6\u2009mA in the pathogenesis of ossification of the posterior longitudinal ligament (OPLL) remains unclear. Tissue samples from OPLL patients and normal posterior longitudinal ligaments were collected, and ligament fibroblastic cells (LFCs) were isolated from OPLL tissues using primary culture. The expression and functional relevance of ALKBH4 in OPLL were investigated through reverse transcription quantitative polymerase chain reaction and western blot analyses. Osteogenic potential was further assessed using alizarin red S staining and alkaline phosphatase activity assays. Methylation status was evaluated by enzyme\u2010linked immunosorbent assay and chromatin immunoprecipitation. Furthermore, the regulatory role of ALKBH4 in LFC ossification was investigated through the bone morphogenetic protein 2 (BMP2) and Wnt\/\u03b2\u2010catenin pathways. ALKBH4 expression was significantly elevated in both OPLL tissues and LFCs, whereas global 6\u2009mA levels and BMP2\u2010associated 6\u2009mA were reduced. Overexpression of ALKBH4 promoted the ossification of LFCs, while its knockdown suppressed osteogenesis. ALKBH4\u2010mediated DNA demethylation at the 6\u2009mA site facilitated Yin Yang 1 (YY1) binding to the BMP2 promoter, enhancing BMP2 transcription and driving ossification. Silencing of BMP2, Wnt\/\u03b2\u2010catenin, or YY1 attenuated the pro\u2010ossification effects of ALKBH4. Furthermore, the mutation that affects the action of ALKBH4 at the 6\u2009mA site fails to induce the osteogenic effect of LFC. These findings demonstrate that ALKBH4 regulates OPLL progression by modulating BMP2 and Wnt\/\u03b2\u2010catenin signaling and by promoting BMP2 transcription through site\u2010specific demethylation in human OPLL tissues and primary LFCs. ALKBH4 may therefore represent a promising therapeutic target for the management of OPLL.<\/jats:p>","DOI":"10.1002\/iub.70121","type":"journal-article","created":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T15:40:35Z","timestamp":1782920435000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>ALKBH4<\/scp>\n                    Promotes Osteogenesis via Epigenetic Regulation of\n                    <scp>BMP2<\/scp>\n                    \u2010Wnt\/\u03b2\u2010Catenin Signaling in Cervical Spine\n                    <scp>OPLL<\/scp>"],"prefix":"10.1002","volume":"78","author":[{"given":"Haiyan","family":"Qiu","sequence":"first","affiliation":[{"name":"Department of Endocrinology, Affiliated Hangzhou First People's Hospital, School of Medicine Westlake University  Zhejiang Hangzhou 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