Stimulation of MMP-1 and CCL2 by NAMPT in PDL Cells

Marjan Nokhbehsaim,Holger Fröhlich,Andreas Jäger,Sigrun Eick,James Deschner,Søren Jepsen,Joni Augusto Cirelli,Andressa Vilas Boas Nogueira,Per Hoffmann,Stefan Herms

doi:10.1155/2013/437123

Abstract

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-1β 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.

Highlights

Periodontitis is a chronic inflammatory disease, which is characterized by the destruction of the tooth-supporting tissues, such as the periodontal ligament (PDL), and caused by pathogenic microorganisms, such as Porphyromonas gingivalis, Tannerella forsythia, Treponema denticola, and Aggregatibacter actinomycetemcomitans
In PDL cells from 10 donors, the results from the microarray analysis were validated by realtime PCR, which confirmed 8 out of the 12 nicotinamide phosphoribosyltransferase (NAMPT)-regulated genes: NAMPT induced a significant upregulation of the mRNA expression for early growth response 1 (EGR1) (2.4-fold), matrixMediators of Inflammation metalloproteinase-1 (MMP-1) (3.8-fold), synaptotagmin 7 (SYT7) (4.6-fold), ITPKA (2.8-fold), CCL2 (2.3-fold), NTM (2.1-fold), insulinlike growth factor 2 mRNA-binding protein 3 (IGF2BP3) (1.9-fold), and neuropilin 1 (NRP1) (1.7-fold)
Our study shows for this first time that NAMPT stimulates the production of CCL2 and MMP-1 in human PDL cells, suggesting that NAMPT may contribute to periodontal inflammation and matrix destruction through the production of these molecules

Summary

Introduction

Periodontitis is a chronic inflammatory disease, which is characterized by the destruction of the tooth-supporting tissues, such as the periodontal ligament (PDL), and caused by pathogenic microorganisms, such as Porphyromonas gingivalis, Tannerella forsythia, Treponema denticola, and Aggregatibacter actinomycetemcomitans. These periodontopathogens can trigger local production of proinflammatory mediators, such as interleukin-1β (IL-1β), cyclooxygenase 2 (COX2), as well as chemokine, cc motif, ligand 2 (CCL2), and matrix-degrading proteases, such as matrix. It has been suggested that increased serum levels of adipokines derived from adipose tissue could make obese individuals more susceptible to periodontitis. This study was established to examine the actions of NAMPT and its regulation by microbial and inflammatory signals in human PDL cells

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Results

Conclusion