Yi Zhang, Yulian Zhang, Yi Chen, Wenzhi Wu, Jianwei Sun, Xiatong Zhang, Jingchen Zhang, Zhuo Chen
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Odontogenic differentiation was assessed using alkaline phosphatase/Alizarin Red staining, while inflammatory mediator production was assessed using RT-qPCR, Western Blot, ELISA, SCENIC and RNA-seq. THP-1 was cultured in conditioned media from ICAM1<sup>+</sup> DPSCs and ICAM1<sup>−</sup> DPSCs. RT-qPCR, Western Blot and flow cytometry were used to assess the proportion of proinflammatory to reparative THP-1. Macrophage-derived cytokines (IL-1β/4/6/10 and TNF-α) were tested for DPSCs to ICAM1<sup>+</sup> differentiation induction.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>Cellular profiling showed a significant increase in ICAM1<sup>+</sup> DPSCs and proinflammatory monocytes in deep carious dental pulp tissue, with ICAM1<sup>+</sup> DPSCs closely interacting with mononuclear macrophages. Immunofluorescence and flow cytometry confirmed the increase in ICAM1<sup>+</sup> DPSCs in deep caries in the affected human and mouse pulp tissue. Alkaline phosphatase and Alizarin Red staining, SCENIC, RT-qPCR, Western Blot and ELISA revealed decreased odontogenic differentiation in ICAM1<sup>+</sup> DPSCs and increased expression of CEBPD, IL-6, CCL2 and CXCL10 in ICAM1<sup>+</sup> DPSC cells. RT-qPCR, Western Blot and flow cytometry indicated an elevated proinflammatory to reparative THP-1 ratio for THP-1 that was cultured in ICAM1<sup>+</sup> DPSC-conditioned media for 1–3 days.</p>\n </section>\n \n <section>\n \n <h3> Conclusions</h3>\n \n <p>During deep caries progression, TNF-α drives the transformation of DPSCs into inflammatory ICAM1<sup>+</sup> DPSCs. This subcluster exhibits impaired odontogenic differentiation capacity, secretes proinflammatory cytokines and chemokines, and enhances macrophage inflammatory activity, contributing to the advancement of deep caries lesions.</p>\n </section>\n </div>","PeriodicalId":13724,"journal":{"name":"International endodontic journal","volume":"58 8","pages":"1184-1196"},"PeriodicalIF":7.1000,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Impact of intercellular adhesion molecule 1-positive dental pulp stem cells in deep caries progression\",\"authors\":\"Yi Zhang, Yulian Zhang, Yi Chen, Wenzhi Wu, Jianwei Sun, Xiatong Zhang, Jingchen Zhang, Zhuo Chen\",\"doi\":\"10.1111/iej.14248\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n \\n <section>\\n \\n <h3> Aim</h3>\\n \\n <p>Dental pulp stem cells (DPSCs) regulate immune responses; however, their heterogeneity in deep caries remains unclear. This study aimed at investigating the role of intercellular adhesion molecule 1-positive DPSCs (ICAM1<sup>+</sup> DPSCs) within the immune microenvironment of deep carious pulp tissue to develop therapeutic strategies.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Methodology</h3>\\n \\n <p>Single-cell sequencing was used to compare cellular profiles between deep caries and healthy pulp tissues. ICAM1<sup>+</sup> DPSCs were quantified using immunofluorescence/flow cytometry in human/mouse models and sorted for functional analyses. Odontogenic differentiation was assessed using alkaline phosphatase/Alizarin Red staining, while inflammatory mediator production was assessed using RT-qPCR, Western Blot, ELISA, SCENIC and RNA-seq. THP-1 was cultured in conditioned media from ICAM1<sup>+</sup> DPSCs and ICAM1<sup>−</sup> DPSCs. RT-qPCR, Western Blot and flow cytometry were used to assess the proportion of proinflammatory to reparative THP-1. Macrophage-derived cytokines (IL-1β/4/6/10 and TNF-α) were tested for DPSCs to ICAM1<sup>+</sup> differentiation induction.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Results</h3>\\n \\n <p>Cellular profiling showed a significant increase in ICAM1<sup>+</sup> DPSCs and proinflammatory monocytes in deep carious dental pulp tissue, with ICAM1<sup>+</sup> DPSCs closely interacting with mononuclear macrophages. Immunofluorescence and flow cytometry confirmed the increase in ICAM1<sup>+</sup> DPSCs in deep caries in the affected human and mouse pulp tissue. Alkaline phosphatase and Alizarin Red staining, SCENIC, RT-qPCR, Western Blot and ELISA revealed decreased odontogenic differentiation in ICAM1<sup>+</sup> DPSCs and increased expression of CEBPD, IL-6, CCL2 and CXCL10 in ICAM1<sup>+</sup> DPSC cells. RT-qPCR, Western Blot and flow cytometry indicated an elevated proinflammatory to reparative THP-1 ratio for THP-1 that was cultured in ICAM1<sup>+</sup> DPSC-conditioned media for 1–3 days.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Conclusions</h3>\\n \\n <p>During deep caries progression, TNF-α drives the transformation of DPSCs into inflammatory ICAM1<sup>+</sup> DPSCs. This subcluster exhibits impaired odontogenic differentiation capacity, secretes proinflammatory cytokines and chemokines, and enhances macrophage inflammatory activity, contributing to the advancement of deep caries lesions.</p>\\n </section>\\n </div>\",\"PeriodicalId\":13724,\"journal\":{\"name\":\"International endodontic journal\",\"volume\":\"58 8\",\"pages\":\"1184-1196\"},\"PeriodicalIF\":7.1000,\"publicationDate\":\"2025-05-08\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"International endodontic journal\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1111/iej.14248\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"DENTISTRY, ORAL SURGERY & MEDICINE\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"International endodontic journal","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1111/iej.14248","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"DENTISTRY, ORAL SURGERY & MEDICINE","Score":null,"Total":0}
Impact of intercellular adhesion molecule 1-positive dental pulp stem cells in deep caries progression
Aim
Dental pulp stem cells (DPSCs) regulate immune responses; however, their heterogeneity in deep caries remains unclear. This study aimed at investigating the role of intercellular adhesion molecule 1-positive DPSCs (ICAM1+ DPSCs) within the immune microenvironment of deep carious pulp tissue to develop therapeutic strategies.
Methodology
Single-cell sequencing was used to compare cellular profiles between deep caries and healthy pulp tissues. ICAM1+ DPSCs were quantified using immunofluorescence/flow cytometry in human/mouse models and sorted for functional analyses. Odontogenic differentiation was assessed using alkaline phosphatase/Alizarin Red staining, while inflammatory mediator production was assessed using RT-qPCR, Western Blot, ELISA, SCENIC and RNA-seq. THP-1 was cultured in conditioned media from ICAM1+ DPSCs and ICAM1− DPSCs. RT-qPCR, Western Blot and flow cytometry were used to assess the proportion of proinflammatory to reparative THP-1. Macrophage-derived cytokines (IL-1β/4/6/10 and TNF-α) were tested for DPSCs to ICAM1+ differentiation induction.
Results
Cellular profiling showed a significant increase in ICAM1+ DPSCs and proinflammatory monocytes in deep carious dental pulp tissue, with ICAM1+ DPSCs closely interacting with mononuclear macrophages. Immunofluorescence and flow cytometry confirmed the increase in ICAM1+ DPSCs in deep caries in the affected human and mouse pulp tissue. Alkaline phosphatase and Alizarin Red staining, SCENIC, RT-qPCR, Western Blot and ELISA revealed decreased odontogenic differentiation in ICAM1+ DPSCs and increased expression of CEBPD, IL-6, CCL2 and CXCL10 in ICAM1+ DPSC cells. RT-qPCR, Western Blot and flow cytometry indicated an elevated proinflammatory to reparative THP-1 ratio for THP-1 that was cultured in ICAM1+ DPSC-conditioned media for 1–3 days.
Conclusions
During deep caries progression, TNF-α drives the transformation of DPSCs into inflammatory ICAM1+ DPSCs. This subcluster exhibits impaired odontogenic differentiation capacity, secretes proinflammatory cytokines and chemokines, and enhances macrophage inflammatory activity, contributing to the advancement of deep caries lesions.
期刊介绍：
The International Endodontic Journal is published monthly and strives to publish original articles of the highest quality to disseminate scientific and clinical knowledge; all manuscripts are subjected to peer review. Original scientific articles are published in the areas of biomedical science, applied materials science, bioengineering, epidemiology and social science relevant to endodontic disease and its management, and to the restoration of root-treated teeth. In addition, review articles, reports of clinical cases, book reviews, summaries and abstracts of scientific meetings and news items are accepted.
The International Endodontic Journal is essential reading for general dental practitioners, specialist endodontists, research, scientists and dental teachers.
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