International endodontic journal · 2025
Impact of intercellular adhesion molecule 1-positive dental pulp stem cells in deep caries progression.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Zhang Yi, Zhang Yulian, Chen Yi, Wu Wenzhi, Sun Jianwei, Zhang Xiatong, Zhang Jingchen, Chen Zhuo
Аннотация
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.
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.