{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T08:12:46Z","timestamp":1788509566787,"version":"build-2803163510"},"reference-count":47,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T00:00:00Z","timestamp":1788480000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T00:00:00Z","timestamp":1788480000000},"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":["82470964"],"award-info":[{"award-number":["82470964"]}],"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":["82270964"],"award-info":[{"award-number":["82270964"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Int Endodontic J"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>Pulpitis is a common and painful disease characterised by complex and dynamic immune responses and may lead to irreversible tissue damage or tooth loss. Macrophages act as key sentinels that exhibit differential metabolic reprogramming, tightly orchestrating the immune microenvironment. However, the specific metabolic mechanisms governing macrophage\u2010driven inflammatory activation in pulpitis remain unclear. Here, we reveal a specific lipid metabolism\u2010driven immune pathway within macrophages in pulpitis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methodology<\/jats:title>\n                    <jats:p>An integrative analysis of single\u2010cell RNA sequencing (scRNA\u2010seq), lipidomics and bulk RNA sequencing (RNA\u2010seq) was employed to characterise macrophage subpopulations and metabolic alterations in pulpitis. Western blot and immunofluorescence staining were performed to validate the expression of phospholipase A2 group VII (PLA2G7) in human pulp tissues. In\u00a0vitro, an inflammatory THP\u20101 macrophage model was established to investigate the effects of PLA2G7 inhibition and lysophosphatidylcholine (LPC) supplementation, and macrophage inflammatory activation was assessed by RT\u2010qPCR, Western blot, ELISA and immunofluorescence staining. Bioinformatic analyses and fluorescence recovery after photobleaching (FRAP) experiments were conducted to identify the upstream transcriptional regulator of PLA2G7 and explore its regulatory mechanism. A murine pulpitis model treated with the PLA2G7 inhibitor darapladib was used to evaluate the anti\u2010inflammatory effects by ELISA, immunohistochemical and immunofluorescence staining.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>ScRNA\u2010seq, lipidomics and RNA\u2010seq analyses identified a distinct lipid\u2010associated macrophage subset with high PLA2G7 expression in pulpitis. The abundance of this subset increased with inflammatory severity. Immunofluorescence and Western blot validated increased PLA2G7 expression in lipid\u2010associated macrophages in pulpitis tissues. In\u00a0vitro, inhibition of PLA2G7 significantly suppressed inflammatory responses, whereas supplementation with LPC attenuated this anti\u2010inflammatory effect. In\u00a0vivo, darapladib\u2010mediated inhibition of PLA2G7 significantly attenuated pulpitis progression and reduced macrophage activation in mice. Mechanistically, integrative bioinformatic analysis identified JunD proto\u2010oncogene (JUND) as a transcriptional regulator of PLA2G7, potentially via liquid\u2013liquid phase separation (LLPS)\u2010mediated transcriptional condensates.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These findings identify PLA2G7 as a potential biomarker for pulpitis and reveal a JUND\u2010PLA2G7\u2010LPC signalling axis linking lipid metabolism to macrophage\u2010mediated inflammatory responses, providing a novel perspective for preserving dental pulp vitality.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/iej.70264","type":"journal-article","created":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T07:22:06Z","timestamp":1788506526000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>PLA2G7<\/scp>\n                    \u2010Mediated Pro\u2010Inflammatory Activation of Lipid\u2010Associated Macrophages Drives Pulpitis"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-3305-1434","authenticated-orcid":false,"given":"Xinyi","family":"Chen","sequence":"first","affiliation":[{"name":"Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine Zhejiang Provincial Clinical Research Center for Oral Diseases, Zhejiang Key Laboratory of Oral Biomedical, Zhejiang\u2010Singapore International Joint Laboratory of Oral Bioengineering, Zhejiang Clinovation Pride  Hangzhou 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