NAMPT Is an Essential Regulator of RA-Mediated Periodontal Inflammation.
Recent studies have indicated a potential correlation between rheumatoid arthritis (RA) and periodontal inflammation. We undertook this study to verify whether RA mediates periodontitis-like phenotypes in experimental mouse models of RA and to explore the role of nicotinamide phosphoribosyltransferase (NAMPT) in periodontal inflammation during RA pathogenesis. Periodontal inflammation and alveolar bone loss have been reported in mice with collagen-induced arthritis (CIA) and in genetically modified tumor necrosis factor-α (TNF-α) transgenic (TG) mouse models. Among the adipokines examined in our study, NAMPT expression was markedly upregulated in the periodontal ligament (PDL) tissues in RA mouse models and in human PDL cells stimulated by the proinflammatory cytokines, interleukin (IL) 1β and TNF-α. When NAMPT was overexpressed with the Nampt-synthesizing adenovirus vector (Ad- Nampt), the PDL cells exhibited an increased expression of cytokines (IL6), chemokines (IL8 and chemokine [C-C motif] ligand 5 [CCL5]), inflammatory mediators (cyclooxygenase 2 [COX-2]), and matrix-degrading enzymes (matrix metalloproteinase [MMP] 1 and MMP3). Inhibition of NAMPT by the intracellular NAMPT (iNAMPT) inhibitor, FK866, or by the sirtuin inhibitor, nicotinamide, in PDL cells led to inhibition of the IL1β or Ad- Nampt-induced upregulation of catabolic factors, whereas treatment with recombinant NAMPT protein or blockade of extracellular NAMPT (eNAMPT) with blocking antibody did not. Moreover, NAMPT inhibition by the intraperitoneal or intragingival injection of FK866 in CIA mice inhibited periodontal tissue damage, under conditions of RA. Thus, our results verified the co-occurrence of RA and periodontal inflammation using experimental mouse models of RA, suggesting that iNAMPT in PDL cells plays a pivotal role in the pathogenesis of RA-mediated periodontal inflammation by regulating the expression levels of catabolic genes, such as IL6, IL8, CCL5, COX-2, MMP1, and MMP3.
1 Department of Pharmacology and Dental Therapeutics, School of Dentistry, Chonnam National University, Gwangju, Republic of Korea.|2 Research Center for Biomineralization Disorders, School of Dentistry, Chonnam National University, Gwangju, Republic of Korea.
D
D
Kim
3 Bioimaging and Cell Logistics Research Center, School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju, Republic of Korea.
G
G
Lee
3 Bioimaging and Cell Logistics Research Center, School of Life Sciences, Gwangju Institute of Science and Technology, Gwangju, Republic of Korea.
Y H
YH
Huh
1 Department of Pharmacology and Dental Therapeutics, School of Dentistry, Chonnam National University, Gwangju, Republic of Korea.|2 Research Center for Biomineralization Disorders, School of Dentistry, Chonnam National University, Gwangju, Republic of Korea.
S Y
SY
Lee
1 Department of Pharmacology and Dental Therapeutics, School of Dentistry, Chonnam National University, Gwangju, Republic of Korea.|2 Research Center for Biomineralization Disorders, School of Dentistry, Chonnam National University, Gwangju, Republic of Korea.
K H
KH
Park
2 Research Center for Biomineralization Disorders, School of Dentistry, Chonnam National University, Gwangju, Republic of Korea.
S
S
Kim
4 Department of Pediatric Dentistry, School of Dentistry, Chonnam National University, Gwangju, Republic of Korea.
J
J
Kim
1 Department of Pharmacology and Dental Therapeutics, School of Dentistry, Chonnam National University, Gwangju, Republic of Korea.|2 Research Center for Biomineralization Disorders, School of Dentistry, Chonnam National University, Gwangju, Republic of Korea.
J
J
Koh
1 Department of Pharmacology and Dental Therapeutics, School of Dentistry, Chonnam National University, Gwangju, Republic of Korea.|2 Research Center for Biomineralization Disorders, School of Dentistry, Chonnam National University, Gwangju, Republic of Korea.
J
J
Ryu
D000818:Animals; D000842:Ankle / Q000000981:diagnostic imaging; D001169:Arthritis, Experimental / Q000378:metabolism; D001172:Arthritis, Rheumatoid / Q000378:metabolism*; D015153:Blotting, Western; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D007249:Inflammation / Q000378:metabolism; D008297:Male; D008437:Maxilla / Q000000981:diagnostic imaging; D051379:Mice; D008822:Mice, Transgenic; D054409:Nicotinamide Phosphoribosyltransferase / Q000502:physiology*; D010518:Periodontitis / Q000378:metabolism*; D010641:Phenotype; D016133:Polymerase Chain Reaction; D055114:X-Ray Microtomography
D054409:Nicotinamide Phosphoribosyltransferase
adipokines; arthritis; bone; chemokines; cytokines; periodontitis