Department of Restorative Dentistry and Endodontology, Osaka University Graduate School of Dentistry, 1-8 Yamadaoka Suita, Osaka, 565-0871, Japan.
Department of Oral Anatomy and Developmental Biology, Osaka University Graduate School of Dentistry, Osaka, Japan.
Sci Rep. 2021 Oct 4;11(1):19673. doi: 10.1038/s41598-021-99231-x.
Various disease-related genes have recently been identified using single nucleotide polymorphisms (SNPs). This study identified disease-related genes by analyzing SNP using genomic DNA isolated from Japanese patients with periapical periodontitis. Results showed that the SNP in LRP5 demonstrated a significant genotypic association with periapical lesions (Fisher's exact test, P < 0.05). We constructed an in vivo murine periapical periodontitis model to confirm the Wnt/β-catenin signaling pathway's role in developing and healing periapical periodontitis. We observed that administration of the Wnt/β-catenin signaling pathway inhibitor enlarged the periapical lesion. Moreover, applying lithium chloride (LiCl) to root canals accelerated periapical periodontitis healing. Histological analysis demonstrated that the expression levels of Col1a1 and Runx2 increased in the LiCl application group compared to that in the control group. Furthermore, many CD45R-positive cells appeared in the periapical lesions in the LiCl application group. These results indicated that LiCl promoted the healing of periapical periodontitis by inducing bone formation and immune responses. Our findings suggest that the Wnt/β-catenin signaling pathway regulates the development of periapical periodontitis. We propose a bioactive next-generation root canal treatment agent for this dental lesion.
近年来，通过单核苷酸多态性（SNPs）已鉴定出各种与疾病相关的基因。本研究通过分析从日本根尖周炎患者分离的基因组 DNA 中的 SNP 来鉴定疾病相关基因。结果表明，LRP5 中的 SNP 与根尖病变存在显著的基因型关联（Fisher 确切检验，P<0.05）。我们构建了一种体内小鼠根尖周炎模型，以验证 Wnt/β-catenin 信号通路在根尖周炎发展和愈合中的作用。我们观察到，Wnt/β-catenin 信号通路抑制剂的给药使根尖病变扩大。此外，向根管中施加氯化锂（LiCl）可加速根尖周炎的愈合。组织学分析表明，与对照组相比，LiCl 应用组中 Col1a1 和 Runx2 的表达水平增加。此外，LiCl 应用组的根尖病变中出现了许多 CD45R 阳性细胞。这些结果表明，LiCl 通过诱导骨形成和免疫反应促进根尖周炎的愈合。我们的研究结果表明，Wnt/β-catenin 信号通路调节根尖周炎的发展。我们提出了一种用于该种牙科病变的具有生物活性的下一代根管治疗剂。
