Stimulation of MMP-1 and CCL2 by NAMPT in PDL cells.
Periodontitis is an inflammatory disease caused by pathogenic microorganisms and characterized by the destruction of the periodontium. Obese individuals have an increased risk of periodontitis, and elevated circulating levels of adipokines, such as nicotinamide phosphoribosyltransferase (NAMPT), may be a pathomechanistic link between both diseases. The aim of this in vitro study was to examine the regulation of periodontal ligament (PDL) cells by NAMPT and its production under inflammatory and infectious conditions. NAMPT caused a significant upregulation of 9 genes and downregulation of 3 genes, as analyzed by microarray analysis. Eight of these genes could be confirmed by real-time PCR: NAMPT induced a significant upregulation of EGR1, MMP-1, SYT7, ITPKA, CCL2, NTM, IGF2BP3, and NRP1. NAMPT also increased significantly the MMP-1 and CCL2 protein synthesis. NAMPT was significantly induced by interleukin-1 β and the periodontal microorganism P. gingivalis. NAMPT may contribute to periodontitis through upregulation of MMP-1 and CCL2 in PDL cells. Increased NAMPT levels, as found in obesity, may therefore represent a mechanism whereby obesity could confer an increased risk of periodontitis. Furthermore, microbial and inflammatory signals may enhance the NAMPT synthesis in PDL cells and thereby contribute to the increased gingival and serum levels of this adipokine, as found in periodontitis.
Experimental Dento-Maxillo-Facial Medicine, Center of Dento-Maxillo-Facial Medicine, University of Bonn, 53111 Bonn, Germany.
Marjan
M
Nokhbehsaim
Sigrun
S
Eick
Andressa Vilas Boas
AV
Nogueira
Per
P
Hoffmann
Stefan
S
Herms
Holger
H
Fröhlich
Søren
S
Jepsen
Andreas
A
Jäger
Joni Augusto
JA
Cirelli
James
J
Deschner
D054392:Adipokines / Q000378:metabolism; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D007249:Inflammation; D053583:Interleukin-1beta / Q000378:metabolism; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism*; D054409:Nicotinamide Phosphoribosyltransferase / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D010513:Periodontal Ligament / Q000166:cytology*; D010518:Periodontitis / Q000378:metabolism / Q000473:pathology; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction; D015854:Up-Regulation
D054392:Adipokines; C111835:CCL2 protein, human; D018932:Chemokine CCL2; D053583:Interleukin-1beta; D054409:Nicotinamide Phosphoribosyltransferase; C522360:MMP1 protein, human; D020781:Matrix Metalloproteinase 1