{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T08:09:46Z","timestamp":1776240586580,"version":"3.50.1"},"reference-count":37,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T00:00:00Z","timestamp":1768780800000},"content-version":"vor","delay-in-days":18,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"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":["Journal Cellular Physiology"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Periodontitis is a predominant persistent inflammatory disease marked by consistent destruction of tooth\u2010supporting tissues including periodontal ligament and alveolar bone. Although some cytokines have been identified as key mediators, the upstream regulatory molecules that drives this pathological bone loss remains elusive. This study explores the mechanistic role of lncRNA ZFAS1 in the dysregulated bone remodeling of periodontitis microenvironment. We utilized single\u2010cell and bulk RNA sequencing to profile cellular and molecular landscape in healthy and diseased periodontal tissues. GSEA analysis of bulk transcriptomes confirmed a significant activation of osteoclast\u2010related pathways in disease (NES\u2009=\u20091.7, FDR q\u2009=\u20090.025). Findings were validated through qPCR, histology, and immunohistochemistry. The gain\u2010 and loss\u2010of\u2010function models in RAW264.7 and MC3T3\u2010E1 cells to characterize the role of lncRNA ZFAS1 in vitro. The scRNA\u2010seq analysis unveiled a marked 11\u2010fold increase in osteoclast\u2010osteoblast ratio in periodontitis, which was further confirmed histologically. This shift was accompanied by a specific inflammatory profile, and a marked upregulation of lncRNA ZFAS1 in diseased tissues. Notably, ZFAS1 expression showed a robust positive correlation with early osteoclast marker genes NFATC1 (R\n                    <jats:sup>2<\/jats:sup>\n                    \u2009=\u20090.2056,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.015) and TRAP1 (R\n                    <jats:sup>2<\/jats:sup>\n                    \u2009=\u20090.784,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.0001) but not the late\u2010stage effector CTSK (R\n                    <jats:sup>2<\/jats:sup>\n                    \u2009=\u20090.0011,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.792). We confirmed that lncRNA ZFAS1 expression was precisely induced by the synergetic effect of differentiation (RANKL) and inflammatory (LPS) signals. Functionally, lncRNA ZFAS1 overexpression in RAW264.7 potentiated osteoclastogenesis, enhanced TRAP\u2010positive osteoclasts and increased resorptive gene expression (NFATC1, Dcstamp, ACP5, CTSK, V\u2010ATPase d2), while its knockdown exhibited the opposite effect. In contrast, lncRNA ZFAS1 knockdown in MC3T3\u2010E1 boosted differentiation and matrix mineralization, augmented osteoblast\u2010related gene expression (Runx2, ALP, OCN). In summary, lncRNA ZFAS1 is a critical driver of inflammatory bone loss, functioning as a dual\u2010path regulator that promotes osteoclastogenesis and inhibits osteoblastogenesis. Its physiological role as a negative osteogenic regulator is evidenced by its downregulation during normal differentiation, highlighting its therapeutic potential for periodontitis and related conditions.\n                  <\/jats:p>","DOI":"10.1002\/jcp.70134","type":"journal-article","created":{"date-parts":[[2026,1,19]],"date-time":"2026-01-19T08:01:56Z","timestamp":1768809716000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["LncRNA ZFAS1 Promotes Alveolar Bone Resorption by Enhancing Osteoclastogenesis in Periodontitis"],"prefix":"10.1002","volume":"241","author":[{"given":"Lilliane","family":"Aol","sequence":"first","affiliation":[{"name":"Key Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology Huazhong University of Science and Technology  Wuhan 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