Abstract：
OBJECTIVE: This study sought to explore the role of developmental endothelial locus-1 (DEL-1) in osteogenic differentiation of human periodontal ligament stem cells (hPDLSCs) and investigate the therapeutic effect of DEL-1 in ligature-induced experimental periodontitis with type 2 diabetes mellitus (T2DM).
BACKGROUND: T2DM is a significant risk factor for periodontitis. Treatment modalities for periodontitis with T2DM are being explored. DEL-1 is a versatile protein that can modulate the different stages of inflammatory diseases including periodontitis. The direct effect of DEL-1 on osteogenic differentiation of PDLSCs in periodontitis with T2DM is poorly understood.
METHODS: Primary hPDLSCs were isolated from periodontal ligament tissue and identified by flow cytometry. In osteogenesis experiments, alkaline phosphatase (ALP), Alizarin Red staining and western blot were used to assess the osteogenic effect of DEL-1 on hPDLSCs in high glucose and inflammation environments. The mouse model of ligature-induced experimental periodontitis was established. H&E and Masson\'s trichrome staining were used to assess the change of periodontal tissue after local periodontal injection of DEL-1. Immunohistochemical staining was used to evaluate osteogenic-related protein expression.
RESULTS: hPDLSCs expressed mesenchymal stem cell (MSC)-specific surface markers and were negative for hematopoietic cell surface markers. hPDLSCs had the potential for multidirectional differentiation. DEL-1 could enhance the osteogenic differentiation of hPDLSCs in high glucose and inflammation environments, although it did not return to the control level. Histological staining showed that DEL-1 contributed to alveolar bone regeneration and osteogenic-related protein expression, but the degree of improvement in T2DM mice was lower than in non-T2DM mice.
CONCLUSIONS: In summary, we demonstrated that DEL-1 could promote osteogenic differentiation of hPDLSCs in high glucose and inflammation environment and rescue alveolar bone loss in experimental periodontitis with T2DM, which could provide a novel therapeutic target for periodontitis with T2DM.
BACKGROUND: T2DM is a significant risk factor for periodontitis. Treatment modalities for periodontitis with T2DM are being explored. DEL-1 is a versatile protein that can modulate the different stages of inflammatory diseases including periodontitis. The direct effect of DEL-1 on osteogenic differentiation of PDLSCs in periodontitis with T2DM is poorly understood.
METHODS: Primary hPDLSCs were isolated from periodontal ligament tissue and identified by flow cytometry. In osteogenesis experiments, alkaline phosphatase (ALP), Alizarin Red staining and western blot were used to assess the osteogenic effect of DEL-1 on hPDLSCs in high glucose and inflammation environments. The mouse model of ligature-induced experimental periodontitis was established. H&E and Masson\'s trichrome staining were used to assess the change of periodontal tissue after local periodontal injection of DEL-1. Immunohistochemical staining was used to evaluate osteogenic-related protein expression.
RESULTS: hPDLSCs expressed mesenchymal stem cell (MSC)-specific surface markers and were negative for hematopoietic cell surface markers. hPDLSCs had the potential for multidirectional differentiation. DEL-1 could enhance the osteogenic differentiation of hPDLSCs in high glucose and inflammation environments, although it did not return to the control level. Histological staining showed that DEL-1 contributed to alveolar bone regeneration and osteogenic-related protein expression, but the degree of improvement in T2DM mice was lower than in non-T2DM mice.
CONCLUSIONS: In summary, we demonstrated that DEL-1 could promote osteogenic differentiation of hPDLSCs in high glucose and inflammation environment and rescue alveolar bone loss in experimental periodontitis with T2DM, which could provide a novel therapeutic target for periodontitis with T2DM.
摘要：
目的：本研究旨在探讨发育内皮位点-1(DEL-1)在人牙周膜干细胞(hPDLSCs)成骨分化中的作用，并探讨DEL-1在结扎诱导的实验性2型糖尿病(T2DM)牙周炎中的治疗作用。
背景：T2DM是牙周炎的重要危险因素。正在探索T2DM牙周炎的治疗方式。DEL-1是一种多功能蛋白，可以调节包括牙周炎在内的炎性疾病的不同阶段。DEL-1对牙周炎伴T2DM患者PDLSCs成骨分化的直接感化尚不清楚。
方法：从牙周膜组织中分离原代hPDLSCs，流式细胞术鉴定。在成骨实验中,碱性磷酸酶(ALP),使用茜素红染色和蛋白质印迹来评估DEL-1在高糖和炎症环境中对hPDLSCs的成骨作用。建立结扎诱导实验性牙周炎小鼠模型。采用H&E和Masson三色染色法评价牙周局部注射DEL-1后牙周组织的变化。免疫组织化学染色用于评估成骨相关蛋白的表达。
结果：hPDLSCs表达间充质干细胞（MSC）特异性表面标志物，造血细胞表面标志物阴性。hPDLSCs具有多向分化的潜能。DEL-1可以增强hPDLSCs在高糖和炎症环境中的成骨分化,尽管它没有回到控制水平。组织学染色显示DEL-1促进牙槽骨再生和成骨相关蛋白表达,但T2DM小鼠的改善程度低于非T2DM小鼠。
结论：总之，我们证明DEL-1可以促进hPDLSCs在高糖和炎症环境中的成骨分化，挽救实验性牙周炎伴T2DM的牙槽骨丢失，为T2DM牙周炎的治疗提供了新的靶点。
背景：T2DM是牙周炎的重要危险因素。正在探索T2DM牙周炎的治疗方式。DEL-1是一种多功能蛋白，可以调节包括牙周炎在内的炎性疾病的不同阶段。DEL-1对牙周炎伴T2DM患者PDLSCs成骨分化的直接感化尚不清楚。
方法：从牙周膜组织中分离原代hPDLSCs，流式细胞术鉴定。在成骨实验中,碱性磷酸酶(ALP),使用茜素红染色和蛋白质印迹来评估DEL-1在高糖和炎症环境中对hPDLSCs的成骨作用。建立结扎诱导实验性牙周炎小鼠模型。采用H&E和Masson三色染色法评价牙周局部注射DEL-1后牙周组织的变化。免疫组织化学染色用于评估成骨相关蛋白的表达。
结果：hPDLSCs表达间充质干细胞（MSC）特异性表面标志物，造血细胞表面标志物阴性。hPDLSCs具有多向分化的潜能。DEL-1可以增强hPDLSCs在高糖和炎症环境中的成骨分化,尽管它没有回到控制水平。组织学染色显示DEL-1促进牙槽骨再生和成骨相关蛋白表达,但T2DM小鼠的改善程度低于非T2DM小鼠。
结论：总之，我们证明DEL-1可以促进hPDLSCs在高糖和炎症环境中的成骨分化，挽救实验性牙周炎伴T2DM的牙槽骨丢失，为T2DM牙周炎的治疗提供了新的靶点。
