A critical role for suppressors of cytokine signaling 3 in regulating LPS-induced transcriptional activation of matrix metalloproteinase-13 in osteoblasts

Gao, Anqi; Kantarcı, Alpdoğan; Herrera, Bruno S.; Gao, Hongwei; Dyke, Thomas E. Van

doi:10.7717/peerj.51

Cited by 19 publications

(22 citation statements)

References 43 publications

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“…Gao et al [34] used Escherichia coli LPS to stimulate osteoblasts. They found that LPS is another stimulator inducing the transcriptional activation of MMP-13.…”

Section: Discussionmentioning

confidence: 99%

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

Liu

Qiu

et al. 2017

Journal of Oral Microbiology

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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.

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“…Gao et al [34] used Escherichia coli LPS to stimulate osteoblasts. They found that LPS is another stimulator inducing the transcriptional activation of MMP-13.…”

Section: Discussionmentioning

confidence: 99%

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

Liu

Qiu

et al. 2017

Journal of Oral Microbiology

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“…Neonatal mouse calvarial osteoblasts were isolated from litters (7–8 mice) by dissection of the scalp skin and removal of the calvariae as previously described [35]. Ascorbic acid (50 µg/ml) and β-glycerophosphate (10 mM) were added to the medium every other day for 10 days to allow osteoblast differentiation.…”

Section: Methodsmentioning

confidence: 99%

Testosterone Regulates Bone Response to Inflammation

Steffens

Herrera²,

Coimbra

et al. 2014

Horm Metab Res

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This study evaluated the alveolar bone response to testosterone and the impact of Resolvin D2 (RvD2) on testosterone-induced osteoblast function. For the in vivo characterization, 60 male adult rats were used. Treatments established sub-physiologic (L), normal (N), or supra-physiologic (H) concentrations of testosterone. Forty rats were subjected to orchiectomy; 20 rats received periodical testosterone injections while 20 rats received testicular sham-operation. Four weeks after the surgeries, 10 rats in each group received a subgingival ligature around the lower first molars to induce experimental periodontal inflammation and bone loss. In parallel, osteoblasts were differentiated from neonatal mice calvariae and treated with various doses of testosterone for 48 h. Cell lysates and conditioned media were used for the determination of alkaline phosphatase, osteocalcin, RANKL, and osteoprotegerin. Micro-computed tomography linear analysis demonstrated that bone loss was significantly increased for both L and H groups compared to animals with normal levels of testosterone. Gingival IL-1β expression was increased in the L group (p < 0.05). Ten nM testosterone significantly decreased osteocalcin, RANKL, and OPG levels in osteoblasts; 100 nM significantly increased the RANKL:OPG ratio. RvD2 partially reversed the impact of 10 nM testosterone on osteocalcin, RANKL, and OPG. These findings suggest that both L and H testosterone levels increase inflammatory bone loss in male rats. While low testosterone predominantly increases the inflammatory response, high testosterone promotes a higher osteoblast-derived RANKL:OPG ratio. The proresolving mediator RvD2 ameliorates testosterone-derived downregulation of osteocalcin, RANKL, and OPG in primary murine osteoblasts suggesting a direct role of inflammation in osteoblast function.

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“…All SOCS proteins share a central SRC-homology 2 (SH2) domain, an amino-terminal domain of variable length and sequence, and a conserved SOCS box at the C-terminus [ 23 ]. Specifically, SOCS1 and SOCS3 take part in a negative feedback loop to attenuate inflammatory responses in osteoblasts [ 24 , 25 ]. Current studies demonstrated that resveratrol is able to alleviate the inflammatory responses of LPS-stimulated macrophages and microglial cells via SOCS1, as a negative regulator of cytokine signaling [ 26 , 27 ].…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2018

Molecules

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Porphyromonas endodontalis (P. endodontalis) lipopolysaccharide (LPS) is associated with the progression of bone resorption in periodontal and periapical diseases. Matrix metalloproteinase-2 (MMP-2) expression and activity are elevated in apical periodontitis and have been suggested to participate in bone resorption. Therefore, inhibiting MMP-2 activation may be considered a therapeutic strategy for treating apical periodontitis. Resveratrol is a natural non-flavonoid polyphenol that has been reported to have antioxidant, anti-cancer, and anti-inflammatory properties. However, the capacity of resveratrol to protect osteoblast cells from P. endodontalis LPS insults and the mechanism of its inhibitory effects on MMP-2 activation is poorly understood. Here, we demonstrate that cell viability is unchanged when 10 mg L−1 P. endodontalis LPS is used, and MMP-2 expression is drastically induced by P. endodontalis LPS in a concentration- and time-dependent manner. Twenty micromolar resveratrol did not reduce MC3T3-E1 cell viability. Resveratrol increased AMP-activated protein kinase (AMPK) phosphorylation, and Compound C, a specific AMPK inhibitor, partially abolished the resveratrol-mediated phosphorylation of AMPK. In addition, AMPK inhibition blocked the effects of resveratrol on MMP-2 expression and activity in LPS-induced MC3T3-E1 cells. Treatment with resveratrol also induced suppressor of cytokine signaling 1 (SOCS1) expression in MC3T3-E1 cells. SOCS1 siRNA negated the inhibitory effects of resveratrol on LPS-induced MMP-2 production. Additionally, resveratrol-induced SOCS1 upregulation was reduced by treatment with compound C. These results demonstrate that AMPK and SOCS1 activation are important signaling events during resveratrol-mediated inhibition of MMP-2 production in response to LPS in MC3T3-E1 cells, and there is crosstalk between AMPK and SOCS1 signaling.

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A critical role for suppressors of cytokine signaling 3 in regulating LPS-induced transcriptional activation of matrix metalloproteinase-13 in osteoblasts

Cited by 19 publications

References 43 publications

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

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

Testosterone Regulates Bone Response to Inflammation

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

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