Activation of hypoxia-inducible factor 1 attenuates periapical inflammation and bone loss.
10.1038/s41368-018-0015-0
- Author:
Kimito HIRAI
1
;
Hisako FURUSHO
2
;
Kiichi HIROTA
3
;
Hajime SASAKI
4
Author Information
1. Department of Cariology, Restorative Sciences & Endodontics, University of Michigan School of Dentistry, Ann Arbor, MI, USA.
2. Department of Oral and Maxillofacial Pathobiology, Hiroshima University, Hiroshima, Hiroshima, Japan.
3. Department of Human Stress Response Science, Institute of Biomedical Science, Kansai Medical University, Hirakata, Osaka, Japan.
4. Department of Cariology, Restorative Sciences & Endodontics, University of Michigan School of Dentistry, Ann Arbor, MI, USA. hajimes@umich.edu.
- Publication Type:Journal Article
- MeSH:
Alveolar Bone Loss;
metabolism;
prevention & control;
Amino Acids, Dicarboxylic;
pharmacology;
Animals;
Cytokines;
metabolism;
Down-Regulation;
Gene Expression;
drug effects;
Hypoxia-Inducible Factor 1, alpha Subunit;
physiology;
Macrophages;
physiology;
Mice;
NF-kappa B;
metabolism;
Osteogenesis;
physiology;
Periapical Periodontitis;
metabolism;
prevention & control;
Real-Time Polymerase Chain Reaction;
X-Ray Microtomography
- From:
International Journal of Oral Science
2018;10(2):12-12
- CountryChina
- Language:English
-
Abstract:
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.
