Sirtuin 1 regulates matrix metalloproteinase-13 expression induced by Porphyromonas endodontalis lipopolysaccharide via targeting nuclear factor–κB in osteoblasts

Abstract

Porphyromonas endodontalis lipopolysaccharide (P.e LPS) is an important initiating factor for periapical inflammation and bone destruction. Matrix metalloproteinase-13 (MMP-13) has been shown to participate in the formation and diffusion of periapical bone lesion in chronic apical periodontitis. Sirtuin 1 (SIRT1) is a key regulator of inflammation in mammalian cells which suppresses the release of inflammatory mediators. This study aimed to explore the role of SIRT1 in regulating MMP-13 expression induced by P.e LPS in osteoblasts. P.e LPS stimulated MMP-13 expression in MC3T3-E1 cells. Knockdown of SIRT1 reinforced the increase of MMP-13mRNA expression induced by P.e LPS. SIRT1 activator resveratrol significantly reduced the expression of MMP-13 and SIRT1 inhibitor EX-527 enhanced the expression of MMP-13. Moreover, SIRT1 activation with resveratrol inhibited acetylation of NF-κB p65 and NF-κB transcriptional activity, which were enhanced by P.e LPS. In addition, NF-κB p65 was involved in P.e LPS-induced MMP-13 expression via directly binding to the MMP-13 promoter. However, SIRT1 activation significantly interfered with this binding. These findings strongly suggest that P.e LPS induces MMP-13 expression in osteoblasts, and SIRT1 suppresses this expression of MMP-13 through targeting NF-κB p65. This provides new insights into understanding the actions of SIRT1 on anti-inflammatory and anti-bone resorption activity.

Resveratrol Suppresses Matrix Metalloproteinase-2 Activation Induced by Lipopolysaccharide in Mouse Osteoblasts via Interactions with AMP-Activated Protein Kinase and Suppressor of Cytokine Signaling 1

“…P. endodontalis , a Gram-negative anaerobic bacteria, is frequently encountered in apical periodontitis with a prevalence of nearly 65% [ 2 ]. Our previous studies demonstrated that the release of a series of pro-inflammatory cytokines induced by P. endodontalis LPS may be related to bone destruction in apical periodontitis [ 5 , 6 , 7 ]. MMP-2 can cleave type IV collagen, specifically, which is a major structural component of the ECM.…”

“…Our previous studies indicated that resveratrol is a potent agonist for SIRT1, and SIRT1 upregulation effectively exerts anti-inflammation molecule expression in osteoblasts [ 7 ]. Resveratrol has previously been reported to regulate SIRT1 by activating AMPK, as AMPK inhibitory activity remarkably abolished resveratrol-induced SIRT1 expression [ 44 ].…”

“…Porphyromonas endodontalis ( P. endodontalis ) is a black pigmented Gram-negative anaerobic microorganism, that is a key pathogen in endodontal infections and apical periodontitis, which is attributed to its high prevalence and pathogenic factors [ 2 , 3 , 4 ]. Lipopolysaccharide (LPS) produced by P. endodontalis triggers the production of a variety of cytokines that participate in bone destruction in the course of apical periodontitis [ 5 , 6 , 7 ]. Matrix metalloproteinase-2 (MMP-2) is a member of MMP family of zinc-dependent endopeptidases that have consistently been shown to be associated with the degradation of the extracellular connective matrix (ECM) and may also be involved in bone destruction [ 8 , 9 ].…”

Prospective, case-controlled study evaluating serum concentration of sirtuin-1 and mannose-binding lectin in patients with and without periodontal and coronary artery disease

“…Studies in periodontal ligament cell cultures have also shown a reduction in proinflammatory substances, such as matrix metalloproteinases and interleukins, a process depen dent, at least in part, on SIRT1 signaling. 49,50 Nonetheless, no studies have analyzed the relationship between serum levels of SIRT1 and MBL, alone or combined, in patients with PD and CAD.…”

Influência do tratamento da doença periodontal na sirtuína 1 e na lectina ligadora de manose em indivíduos com doença arterial coronária

“…179 Humphrey et al 180 188,189,190 Estudos em cultura de células também mostraram redução de substâncias pró-inflamatórias, tais como metaloproteinases de matriz e interleucinas mediada pela SIRT1. 191,192…”