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Subsequently, macrophage\n                      <jats:italic>Atx<\/jats:italic>\n                      knockout (CKO) mice and bone marrow\u2013derived macrophages (BMDMs) were generated to investigate the role of the ATX\/LPA axis in modulating osteoclastogenesis and inflammation during periodontitis development. Finally, the ATX inhibitor PF8380 was used to explore a promising therapeutic strategy for controlling periodontitis. Histomorphological, molecular and cytological analyses were performed using RNA sequencing, real\u2010time polymerase chain reaction, immunofluorescence, immunohistochemistry, enzyme\u2010linked immunosorbent assay, micro\u2010computed tomography, haematoxylin and eosin staining, tartrate\u2010resistant acid phosphatase staining, actin filament staining, pit resorption assay and flow cytometry.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The expression of the ATX\/LPA axis was more enhanced in the periodontitis group than that in the health group and was positively correlated with the severity of periodontitis. Subsequently, CKO mice showed milder inflammation and less bone resorption than wild\u2010type (WT) mice of periodontitis. Following\n                      <jats:styled-content style=\"fixed-case\">\n                        <jats:italic>Porphyromonas gingivalis<\/jats:italic>\n                      <\/jats:styled-content>\n                      LPS stimulation, CKO\u2010BMDMs were markedly suppressed in osteoclastogenesis and inflammation compared to WT\u2010BMDMs. In addition, the mechanism of the ATX\/LPA axis in regulating osteoclastogenesis may act synergistically with activated inflammation\u2010related pathways by RNA sequencing. Finally, we used the ATX inhibitor PF8380 and found that PF8380 alleviated alveolar bone resorption in periodontitis mice and modulated BMDMs' osteoclast differentiation and phenotypic transformation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The ATX\/LPA axis plays a significant regulatory role in osteoclastogenesis and osteoclast activity and may enable selective control of bone loss and inflammation in periodontitis. Therefore, targeting ATX inhibition may represent a novel therapeutic strategy for preventing alveolar bone resorption and periodontal inflammation in patients with periodontitis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/jcpe.70174","type":"journal-article","created":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T07:34:12Z","timestamp":1786692852000},"page":"1735-1747","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Autotaxin\/Lysophosphatidic Acid Axis Promotes Periodontitis by Modulating Macrophage Osteoclastogenesis and Inflammation"],"prefix":"10.1111","volume":"53","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5743-8925","authenticated-orcid":false,"given":"Enyan","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Periodontology Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of Stomatology  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiacheng","family":"Ding","sequence":"additional","affiliation":[{"name":"Department of Periodontology Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of Stomatology  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiting","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Periodontology Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of Stomatology  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-7534-5748","authenticated-orcid":false,"given":"Yining","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Periodontology Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, College of Stomatology, Shanghai Jiao Tong University, National Center for Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology, Shanghai Research Institute of Stomatology  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-8540-222X","authenticated-orcid":false,"given":"Lina","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Periodontology 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