{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T08:06:14Z","timestamp":1790755574136,"version":"4.1.0"},"reference-count":51,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2024,1,27]],"date-time":"2024-01-27T00:00:00Z","timestamp":1706313600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Int Endodontic J"],"published-print":{"date-parts":[[2024,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aim<\/jats:title><jats:p>To investigate novel diagnostic markers for pulpitis and validate by clinical samples from normal and inflamed pulp. To explore the relationship between diagnostic markers and immune cells or their phenotypes during pulp inflammation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methodology<\/jats:title><jats:p>Two microarray datasets, GSE77459 and GSE92681, and identified differential expression genes were integrated. To understand immune features, gene functions, Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Disease Ontology (DO) and ImmuneSigDB Gene Set Enrichment Analysis (GSEA) were analysed. For predictive purposes, machine learning techniques were applied to detect diagnostic markers. Immune infiltration in inflamed pulp was studied using CIBERSORT. The relationship between diagnostic markers and immune cells was investigated and validated their gene expression in clinical samples from the normal or inflamed pulp by qRT\u2010PCR. Finally, the correlation between one marker, secreted phosphoprotein 1 (<jats:italic>SPP1<\/jats:italic>), encoding osteopontin (OPN), and dendritic cells (DCs)\/macrophages was identified via HE staining and multiplex immunohistochemistry. An <jats:italic>in vitro<\/jats:italic> inflammatory dental pulp microenvironment model of THP\u20101 macrophages cocultured with dental pulp cells derived conditioned media (DPCs\u2010CM) to investigate OPN production and macrophage phenotypes was established.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Analysis revealed unique immunologic features in inflamed pulp. Three diagnostic markers for pulpitis: endothelin\u20101 (<jats:italic>EDN1<\/jats:italic>), <jats:italic>SPP1<\/jats:italic>, and purine nucleoside phosphorylase (<jats:italic>PNP<\/jats:italic>), and validated them using qRT\u2010PCR were predicted. Multiplex immunohistochemistry demonstrated OPN co\u2010localized with activated DCs and M2 macrophages during pulp inflammation. <jats:italic>In vitro<\/jats:italic> experiments showed that THP\u20101 macrophages produced the highest levels of OPN when stimulated with DPCs\u2010CM derived from the 20\u2009\u03bcg\/mL LPS pre\u2010conditioned group, suggesting an M2b\u2010like phenotype by increasing surface marker CD86 and expression of <jats:italic>IL6<\/jats:italic>, <jats:italic>TNF\u03b1<\/jats:italic>, <jats:italic>IL10<\/jats:italic>, and <jats:italic>CCL1<\/jats:italic> but not <jats:italic>CCL17<\/jats:italic> and <jats:italic>MerTK<\/jats:italic>. Levels of CCL1 and IL10 elevated significantly in the macrophages' supernatant from the 20\u2009\u03bcg\/mL LPS pre\u2010conditioned CM group. OPN was proven co\u2010localizing with CD86 in the inflamed pulp by immunofluorescence.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The current findings suggest that OPN can serve as a promising biomarker for pulpitis, correlated with DCs and macrophages. OPN<jats:sup><jats:italic>+<\/jats:italic><\/jats:sup> macrophages in the inflamed pulp are associated with M2b\u2010like phenotypes. These insights offer the potential for improved diagnosis and targeted therapy.<\/jats:p><\/jats:sec>","DOI":"10.1111\/iej.14028","type":"journal-article","created":{"date-parts":[[2024,1,27]],"date-time":"2024-01-27T10:27:26Z","timestamp":1706351246000},"page":"464-476","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Osteopontin interacts with dendritic cells and macrophages in pulp inflammation: Comprehensive transcriptomic analysis and laboratory investigations"],"prefix":"10.1111","volume":"57","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7090-3788","authenticated-orcid":false,"given":"Leyi","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Endodontics Shenzhen Stomatology Hospital (Pingshan) of Southern Medical University  Shenzhen Guangdong China"},{"name":"School of Stomatology Southern Medical University  Guangzhou Guangdong 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