Vascular Endothelial Growth Factors and Receptors Are Up-regulated during Development of Apical Periodontitis

Vascular Endothelial Growth Factors and Receptors Are Up-regulated during Development of Apical Periodontitis
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DOI:
10.1016/j.joen.2012.01.005
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发表时间:
2012-05-01
影响因子:
4.2
通讯作者:
Berggreen, Ellen
Berggreen, Ellen
中科院分区:
医学2区
文献类型:
--
作者:
Bletsa, Athanasia;Virtej, Anca;Berggreen, Ellen

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根尖牙周炎是一种常见的炎症性疾病,由持续性根管感染引起,以骨吸收为特征。血管内皮生长因子(VEGFs)及其受体(vegfr)在许多病理和炎症条件下被描述,但它们在根尖牙周炎发展中的参与尚未被彻底研究。本研究的目的是在根尖牙炎大鼠模型中量化基因表达并定位VEGF-A、VEGF-C、VEGF-D、VEGFR-2和VEGFR-3。方法:磨牙单侧暴露于口腔10天或21天。下颌切片采用免疫组化法定位vegf和vegfr,双免疫荧光法鉴定细胞。采用实时定量聚合酶链反应对根尖周围组织进行VEGF-A、VEGF-C和VEGFR-3的基因表达分析。结果:所有研究因子和受体均在对照牙牙周韧带血管中免疫组织化学表达,并在病变发展过程中表达上调。在根尖病变中,巨噬细胞和中性粒细胞表达所有研究的因子和受体,巨噬细胞是VEGF-C和VEGF-D的重要来源。破骨细胞表达VEGFR-2和VEGFR-3,后者也在病变的成纤维细胞样细胞中被发现。第10、21天VEGF-A、VEGFR-3基因表达上调(P < 0.05)。结论:目前的研究结果表明,在疾病发展过程中,VEGF家族和受体参与了血管重塑和免疫功能。破骨细胞中VEGFR-2和VEGFR-3的存在表明骨吸收活性受到vegf的影响。[J] end2012;38:628-635 .]
Introduction: Apical periodontitis is a common inflammatory disease caused by persistent root canal infection and is characterized by bone resorption. Vascular endothelial growth factors (VEGFs) and their receptors (VEGFRs) have been described in many pathologic and inflammatory conditions, but their involvement in the development of apical periodontitis has not been thoroughly investigated. The aim of this study was to quantify gene expression and localize VEGF-A, VEGF-C, and VEGF-D and VEGFR-2 and VEGFR-3 in a rat model of apical periodontitis. Methods: Molar pulps were unilaterally exposed to the oral cavity for 10 or 21 days. Jaw sections were used for localization of VEGFs and VEGFRs with immunohistochemistry and identification of cells with double immunofluorescence. Gene expression analysis for VEGF-A, VEGF-C, and VEGFR-3 of periapical tissues was performed with quantitative real-time polymerase chain reaction. Results: All investigated factors and receptors were expressed immunohistochemically in blood vessels at the periodontal ligament of control teeth and were up-regulated during lesion development. In apical lesions, macrophages and neutrophils expressed all studied factors and receptors, with macrophages being an important source of VEGF-C and VEGF-D. Osteoclasts expressed VEGFR-2 and VEGFR-3, and the latter was also identified in fibroblast-like cells in the lesions. VEGF-A and VEGFR-3 gene expression was up-regulated at days 10 and 21 (P < .05). Conclusions: The current findings indicate that the VEGF family and receptors are involved in vascular remodeling and immune functions during disease development. The presence of VEGFR-2 and VEGFR-3 on osteoclasts indicates that bone resorbing activity is influenced by VEGFs. (J Endod 2012;38:628-635)