{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,31]],"date-time":"2026-01-31T18:15:24Z","timestamp":1769883324767,"version":"3.49.0"},"reference-count":23,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T00:00:00Z","timestamp":1769731200000},"content-version":"vor","delay-in-days":29,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["International Journal of Endocrinology"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:p>\n                    This study aimed to investigate the role of N\n                    <jats:sup>6<\/jats:sup>\n                    \u2010methyladenosine (m\n                    <jats:sup>6<\/jats:sup>\n                    A) methylation in osteogenic differentiation during osteoporosis (OP). Serum specimens were obtained from 25 individuals diagnosed with OP and 25 age\u2010matched healthy controls. In parallel, MC3T3\u2010E1 preosteoblastic cells were employed for in vitro functional assays. Expression levels of m\n                    <jats:sup>6<\/jats:sup>\n                    A\u2010associated genes were quantified using qPCR. Osteogenic potential was evaluated by measuring ALP activity with an ALP assay kit and by assessing matrix mineralization through Alizarin Red S staining. RIP and dual\u2010luciferase reporter assays were performed to elucidate the molecular interactions involved. To corroborate the in vitro observations, an ovariectomized (OVX) mouse model of OP was established for in vivo validation. The results revealed a significant downregulation of AlkB Homolog 5 (ALKBH5) in both serum samples from OP patients and MC3T3\u2010E1 cells undergoing osteogenic differentiation. Moreover, enforced expression of ALKBH5 suppressed osteogenic differentiation in these cells. Mechanistically, ELK1 was found to be a key downstream effector of ALKBH5. Additionally, YTH domain family protein 2 (YTHDF2) was demonstrated to function as the m\n                    <jats:sup>6<\/jats:sup>\n                    A reader that specifically recognizes the ALKBH5\u2010mediated demethylation site on ELK1 mRNA. Rescue experiments confirmed that ELK1 overexpression or YTHDF2 knockdown promoted osteogenic differentiation, whereas these effects were abolished by ALKBH5 overexpression or ELK1 silencing. In OVX mice, ALKBH5 knockdown mitigated bone loss, improved bone strength, and restored ELK1 expression. Notably, ELK1 inhibition reversed the protective effects of YTHDF2 knockdown on bone loss and mechanical strength in OVX mice. In conclusion, ALKBH5\/YTHDF2 axis might be involved in osteogenic differentiation via regulating ELK1 (a key downstream effector), which might provide a new insight for OP treatment.\n                  <\/jats:p>","DOI":"10.1155\/ije\/2669506","type":"journal-article","created":{"date-parts":[[2026,1,31]],"date-time":"2026-01-31T04:32:39Z","timestamp":1769833959000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["ALKBH5\/YTHDF2 Axis Regulates Osteogenic Differentiation Through Mediating the m\n                    <sup>6<\/sup>\n                    A Modification of 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