Abstract
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/6 J 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.
Highlights
Periodontitis is an inflammatory disease caused by pathogenic oral microorganisms that induce the destruction of periodontal tissue
Bone resorption was initiated at 3 days post-ligation, and Tartrate-resistant acid phosphatase (TRAP)-positive cells, which mark osteoclasts, were increased around the alveolar bone at 8 days post-ligation
Ligation seems to trigger a burst of destruction of the periodontal tissue, and this model may be similar to periodontitis in activated progression phase
Summary
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. Inflamed and damaged tissue, including the gingival epithelium and periodontal connective tissue, produce various inflammatory cytokines[3,4] These inflammatory cytokines break down the homeostasis of periodontal tissues, activate fibroblasts and osteoclasts, and induce loss of connective tissue attachment and alveolar bone[5,6]. Represents rapid bone loss within several days compared to previous models that required oral gavage with high doses of specific bacteria[10,11] and injection of lipopolysaccharide (LPS)[12] In this decade, next-generation sequencing methods for analyzing RNA sequences have been developed and widely performed. This study aimed to identify the DEGs, and investigated the mechanisms underlying rapid periodontal tissue destruction using RNA-seq analysis of ligature-induced periodontitis in mice
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