IADR Abstract Archives
NAMPT is an Essential Catabolic Regulator of RA-mediated Periodontitis
Objectives: Recent study has indicated a potential association between periodontitis (PD) and rheumatoid arthritis (RA). We undertook this study to verify whether RA induces PD-like phenotypes using experimental RA mouse model and to explore the role of nicotinamine phosphoribosyltransferase (NAMPT) on periodontal inflammation during RA pathogenesis.
Methods: PD pathogenesis was determined in Collagen-induced arthritis (CIA), an experimental RA mouse model and evaluated by H&E staining and micro-compute tomography (mCT). Primary cultured periodontal ligament cells (PDL) originated from human were treated with FK-866 for intracellular NAMPT inhibition and anti-NAMPT antibody for extracellular NAMPT inhibition or were infected with adenovirus for NAMPT overexpression. Expression patterns of adipokines and cytokines were determined by immunostaining, western blotting and RT-PCR.
Results: 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, IL1b and TNF-a. 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 CCL5), inflammatory mediators (COX-2), and matrix-degrading enzymes (MMP1 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 IL1b 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.
Conclusions: Our findings verified the co-occurrence of RA and periodontitis using experimental mouse models of RA, suggesting that iNAMPT in PDL cells plays a pivotal role in the pathogenesis of RA-mediated periodontitis by regulating the expression levels of catabolic genes, such as IL6, IL8, CCL5, COX-2, MMP1, and MMP3.
Methods: PD pathogenesis was determined in Collagen-induced arthritis (CIA), an experimental RA mouse model and evaluated by H&E staining and micro-compute tomography (mCT). Primary cultured periodontal ligament cells (PDL) originated from human were treated with FK-866 for intracellular NAMPT inhibition and anti-NAMPT antibody for extracellular NAMPT inhibition or were infected with adenovirus for NAMPT overexpression. Expression patterns of adipokines and cytokines were determined by immunostaining, western blotting and RT-PCR.
Results: 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, IL1b and TNF-a. 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 CCL5), inflammatory mediators (COX-2), and matrix-degrading enzymes (MMP1 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 IL1b 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.
Conclusions: Our findings verified the co-occurrence of RA and periodontitis using experimental mouse models of RA, suggesting that iNAMPT in PDL cells plays a pivotal role in the pathogenesis of RA-mediated periodontitis by regulating the expression levels of catabolic genes, such as IL6, IL8, CCL5, COX-2, MMP1, and MMP3.