Ultrasound microbubble-mediated transfection of NF-κB decoy oligodeoxynucleotide into gingival tissues inhibits periodontitis in rats in vivo.

Hiroyuki Yamaguchi,Risa Usumi-Fujita,Yasuhiro Shimizu,Takashi Ono,Jun Hosomichi,Yuji Ishida,Jun-Ichi Suzuki,Kasumi Hatano,Sawa Kaneko,Sakamuri V Reddy

doi:10.1371/journal.pone.0186264

Hiroyuki Yamaguchi, Risa Usumi-Fujita + Show 8 more

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https://doi.org/10.1371/journal.pone.0186264

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Abstract

Periodontitis is a chronic infectious disease for which the fundamental treatment is to reduce the load of subgingival pathogenic bacteria by debridement. However, previous investigators attempted to implement a nuclear factor kappa B (NF-κB) decoy oligodeoxynucleotide (ODN) as a suppressor of periodontitis progression. Although we recently reported the effectiveness of the ultrasound-microbubble method as a tool for transfecting the NF-κB decoy ODN into healthy rodent gingival tissue, this technique has not yet been applied to the pathological gingiva of periodontitis animal models. Therefore, the aim of this study was to investigate the effectiveness of the technique in transfecting the NF-κB decoy ODN into rats with ligature-induced periodontitis. Micro computed tomography (micro-CT) analysis demonstrated a significant reduction in alveolar bone loss following treatment with the NF-κB decoy ODN in the experimental group. RT-PCR showed that NF-κB decoy ODN treatment resulted in significantly reduced expression of inflammatory cytokine transcripts within rat gingival tissues. Thus, we established a transcutaneous transfection model of NF-κB decoy ODN treatment of periodontal tissues using the ultrasound-microbubble technique. Our findings suggest that the NF-κB decoy ODN could be used as a significant suppressor of gingival inflammation and periodontal disease progression.

Highlights

The funders had no role in study design, data collection and analysis, Periodontitis is a chronic infectious disease that is caused by the accumulation of bacteria, and it leads to the destruction of the surrounding periodontal structure, including pocket deepening, attachment loss, and alveolar bone loss [1]
Subsequent micro-CT analysis of alveolar bone loss detected bone resorption, as evidenced by marked increases in the alveolar bone crest (ABC)–cement enamel junction (CEJ) distances in the mesiodistal direction of the maxillary second molars, in the rats in the P group compared with those in the control group on days 7 and 14 after ligation (Fig 3A and 3B). This distance was reduced in the PUM group compared with that in the P group, and there was no significant difference in the ABC–CEJ distances of the control and PUM groups on days 7 and 14
Toker et al induced periodontitis by binding silk sutures around rat molars and reported that plaque and bacteria accumulation increased in the region where the silk sutures contacted the tissue [29]

Summary

Introduction

The funders had no role in study design, data collection and analysis, Periodontitis is a chronic infectious disease that is caused by the accumulation of bacteria, and it leads to the destruction of the surrounding periodontal structure, including pocket deepening, attachment loss, and alveolar bone loss [1]. The fundamental treatment for periodontitis is still to reduce the load of subgingival pathogenic bacteria by instrumental debridement via surgical or non-surgical approaches [2]. Complete removal of pathogenic biofilms is difficult, as some pathogens are embedded in soft tissues and/or located in anatomically.

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