RNA sequencing for ligature induced periodontitis in mice revealed important role of S100A8 and S100A9 for periodontal destruction
RNA sequencing for ligature induced periodontitis in mice revealed important role of S100A8 and S100A9 for periodontal destruction
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DOI：
10.1038/s41598-019-50959-7
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发表时间：
2019-10-11
影响因子：
4.6
通讯作者：
Izumi, Yuichi
中科院分区：
文献类型：
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作者：
Maekawa, Shogo;Onizuka, Satoru;Izumi, Yuichi
牙周炎是由口腔病原微生物引起牙周组织破坏而引起的炎症性疾病。我们试图通过使用结扎诱导的小鼠牙周炎来鉴定相关的差异表达基因（DEG）并阐明快速牙槽骨流失的机制。将丝结扎在 9 周龄 C57BL/6J 雄性小鼠的上颌左侧第二磨牙周围。体内显微 CT 分析显示，结扎会导致严重的骨质流失。 RNA 测序分析用于检查连接后 3 天的宿主反应，检测到 12,853 个基因，其中每百万个映射读数中每千碱基外显子的片段 >= 1 和 78 DEG。基因本体术语富集分析显示，与中性粒细胞趋化性和炎症反应相关的表达谱在结扎牙龈中显着富集。连接侧的先天免疫反应相关基因（包括 S100a8 和 S100a9）的表达水平显着较高。通过免疫组织化学在连接位点的附着上皮上强烈检测到 S100A8。 S100A8 和 S100A9 表达的抑制表明它们调节 Ca9-22 细胞中 IL1B 和 CTSK 的表达。因此，先天免疫反应相关分子可能与结扎诱发的牙周炎中牙周组织的爆发性破坏有关。特别是，S100A8和S100A9可能在牙槽骨吸收中发挥重要作用。
Periodontitis is an inflammatory disease caused by pathogenic oral microorganisms that induce the destruction of periodontal tissue. We sought to identify the relevant differentially expressed genes (DEGs) and clarify the mechanism underlying the rapid alveolar bone loss by using ligature-induced periodontitis in mice. A silk ligature was tied around the maxillary left second molar in 9-week-old C57BL/6J male mice. In-vivo micro-CT analysis revealed that ligation induced severe bone loss. RNA-sequencing analysis, to examine host responses at 3 days post-ligation, detected 12,853 genes with fragments per kilobase of exon per million mapped reads >= 1, and 78 DEGs. Gene ontology term enrichment analysis revealed the expression profiles related to neutrophil chemotaxis and inflammatory responses were significantly enriched in the ligated gingiva. The expression levels of innate immune response-related genes, including S100a8 and S100a9, were significantly higher in the ligated side. S100A8 was strongly detected by immunohistochemistry at the attached epithelium in ligated sites. Inhibition of S100A8 and S100A9 expression revealed that they regulated IL1B and CTSK expression in Ca9-22 cells. Thus, innate immune response-related molecules might be associated with the burst-destruction of periodontal tissue in ligature-induced periodontitis. Especially, S100A8 and S100A9 may play an important role in alveolar bone resorption.