Abstract
ABSTRACTPorphyromonas 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.
Highlights
Matrix metalloproteinases (MMPs) are a family of hostderived enzymes responsible for degradation of most extracellular matrix proteins [1]
The expression and release of Matrix metalloproteinase-13 (MMP-13) protein were increased by P.e LPS treatment following the increase of time within 24 h, and at 48 h, the expression and release of MMP-13 protein remained at a similar level to the 24 h group, as determined by Western blot (Figure 1(c)) and enzyme-linked immunosorbent assay (ELISA) (Figure 1(d))
The present study demonstrated that P.e LPS stimulated MMP-13 expression in mouse osteoblasts
Summary
Matrix metalloproteinases (MMPs) are a family of hostderived enzymes responsible for degradation of most extracellular matrix proteins [1]. MMP-13 (collagenase-3) belongs to the collagenase subfamily, along with MMP-1 and MMP-8. It is secreted from osteoblasts and macrophages and initiates the degradation of native fibrillar collagen types I, II, and III in bone matrix. These play pivotal roles in bone remodeling activation and pathological bone resorption [3,4]. Emerging evidence suggests that MMP-13 plays a key role in the formation and diffusion of periapical bone lesion in chronic apical periodontitis and the conversion from periapical granuloma to a radicular cyst [8,9,10,11]
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