論文

査読有り 筆頭著者 国際誌
2018年4月13日

Activation of hypoxia-inducible factor 1 attenuates periapical inflammation and bone loss.

International journal of oral science
  • Kimito Hirai
  • ,
  • Hisako Furusho
  • ,
  • Kiichi Hirota
  • ,
  • Hajime Sasaki

10
2
開始ページ
12
終了ページ
12
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1038/s41368-018-0015-0

Hypoxia (low oxygen level) is an important feature during infections and affects the host defence mechanisms. The host has evolved specific responses to address hypoxia, which are strongly dependent on the activation of hypoxia-inducible factor 1 (HIF-1). Hypoxia interferes degradation of HIF-1 alpha subunit (HIF-1α), leading to stabilisation of HIF-1α, heterodimerization with HIF-1 beta subunit (HIF-1β) and subsequent activation of HIF-1 pathway. Apical periodontitis (periapical lesion) is a consequence of endodontic infection and ultimately results in destruction of tooth-supporting tissue, including alveolar bone. Thus far, the role of HIF-1 in periapical lesions has not been systematically examined. In the present study, we determined the role of HIF-1 in a well-characterised mouse periapical lesion model using two HIF-1α-activating strategies, dimethyloxalylglycine (DMOG) and adenovirus-induced constitutively active HIF-1α (CA-HIF1A). Both DMOG and CA-HIF1A attenuated periapical inflammation and tissue destruction. The attenuation in vivo was associated with downregulation of nuclear factor-κappa B (NF-κB) and osteoclastic gene expressions. These two agents also suppressed NF-κB activation and subsequent production of proinflammatory cytokines by macrophages. Furthermore, activation of HIF-1α by DMOG specifically suppressed lipopolysaccharide-stimulated macrophage differentiation into M1 cells, increasing the ratio of M2 macrophages against M1 cells. Taken together, our data indicated that activation of HIF-1 plays a protective role in the development of apical periodontitis via downregulation of NF-κB, proinflammatory cytokines, M1 macrophages and osteoclastogenesis.

リンク情報
DOI
https://doi.org/10.1038/s41368-018-0015-0
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/29654284
PubMed Central
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5966812
ID情報
  • DOI : 10.1038/s41368-018-0015-0
  • PubMed ID : 29654284
  • PubMed Central 記事ID : PMC5966812

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