Emerging Role of PPAR-<i>β</i>/<i>δ</i>in Inflammatory Process Associated to Experimental Periodontitis

Paola, Rosanna Di; Briguglio, Francesco; Paterniti, Irene; Mazzon, Emanuela; Oteri, Giacomo; Militi, David; Cordasco, Gennaro; Cuzzocrea, Salvatore

doi:10.1155/2011/787159

Cited by 28 publications

(27 citation statements)

References 17 publications

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“…The cytosolic and nuclear components in osteoblasts and osteoclast precursors were collected, respectively, as previously described [Wittrant et al, 2008;Di Paola et al, 2011;Zhou et al, 2015]; 20 μg of total protein were loaded on a 10% SDS-PAGE gel and transferred to a nitrocellulose membrane. Runx2, NF-ĸB p65, IKKα/β, phospho-IKKα/β (Ser180/181), IĸBα, phospho-IĸBα (Ser32), pPKAα/β/γ (Thr198), and β-actin were detected using specific primary antibodies from Santa Cruz, CA, USA, and Abcam, Cambridge, UK.…”

Section: Western Blotmentioning

confidence: 99%

Angiotensin II/Angiotensin II Receptor Blockade Affects Osteoporosis via the AT1/AT2-Mediated cAMP-Dependent PKA Pathway

Zhou

Guan

Chen

et al. 2017

Cells Tissues Organs

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Animal studies have reported on the benefits of ARB on bone mass. However, the underlying mechanism for angiotensin II (AngII)/AngII receptor blockade (ARB) in regulating bone mass remains elusive. Since high levels of plasma and urine cAMP are observed in osteoporotic and hypertensive patients, we hypothesized that cAMP may be an important molecule for the downstream events of the activation of AT receptors, members of the G-protein-coupled receptor family, in regulating bone turnover. In this study, micro-CT and X-ray analyses indicated that AngII decreased bone mass via biasing bone resorption over bone formation in osteoporotic mice. However, these adverse effects were blocked by olmesartan and PD123319. In vitro, AngII was shown to downregulate osteogenic differentiation and matrix mineralization, but to upregulate osteoclastic activity by mainly affecting osteoblasts producing osteoclastogenesis-associated key soluble factors, including M-CSF and RANKL. Similarly, ARB treatment exhibited antagonistic effects on AngII. In conclusion, osteoblasts are the directly targeted cells. ARB1 exhibits a greater capacity to increase bone mass than ARB2. The cAMP-dependent PKA pathway plays an important role in AngII/ARB on changing bone mass.

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Section: Western Blotmentioning

confidence: 99%

Angiotensin II/Angiotensin II Receptor Blockade Affects Osteoporosis via the AT1/AT2-Mediated cAMP-Dependent PKA Pathway

Zhou

Guan

Chen

et al. 2017

Cells Tissues Organs

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“…In contrast to PPARα and PPARγ, PPARδ is ubiquitously expressed in diverse cell lineages and is implicated in multiple aspects of biological processes (Neels & Grimaldi, ). A recent study reported that PPARδ exerts an anti‐inflammatory role in experimental periodontitis by attenuating the production of proinflammatory cytokines and the injury of gingivomucosal tissues (Di Paola et al ., ). Activation of PPARδ may induce the expression of extracellular matrix proteins such as collagen I, collagen III, fibronectin, and elastin (Kim et al ., ).…”

Section: Introductionmentioning

confidence: 97%

Peroxisome proliferator‐activated receptor δ inhibits Porphyromonas gingivalis lipopolysaccharide‐induced activation of matrix metalloproteinase‐2 by downregulating NADPH oxidase 4 in human gingival fibroblasts

Yoo

Ham

Hwang

et al. 2015

Molecular Oral Microbiology

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We investigated the roles of peroxisome proliferator-activated receptor δ (PPARδ) in Porphyromonas gingivalis-derived lipopolysaccharide (Pg-LPS)-induced activation of matrix metalloproteinase 2 (MMP-2). In human gingival fibroblasts (HGFs), activation of PPARδ by GW501516, a specific ligand of PPARδ, inhibited Pg-LPS-induced activation of MMP-2 and generation of reactive oxygen species (ROS), which was associated with reduced expression of NADPH oxidase 4 (Nox4). These effects were significantly smaller in the presence of small interfering RNA targeting PPARδ or the specific PPARδ inhibitor GSK0660, indicating that PPARδ is involved in these events. In addition, modulation of Nox4 expression by small interfering RNA influenced the effect of PPARδ on MMP-2 activity, suggesting a mechanism in which Nox4-derived ROS modulates MMP-2 activity. Furthermore, c-Jun N-terminal kinase and p38, but not extracellular signal-regulated kinase, mediated PPARδ-dependent inhibition of MMP-2 activity in HGFs treated with Pg-LPS. Concomitantly, PPARδ-mediated inhibition of MMP-2 activity was associated with the restoration of types I and III collagen to levels approaching those in HGFs not treated with Pg-LPS. These results indicate that PPARδ-mediated downregulation of Nox4 modulates cellular redox status, which in turn plays a critical role in extracellular matrix homeostasis through ROS-dependent regulation of MMP-2 activity.

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“…Because treatment with NF-κB inhibitors impairs agonistinduced platelet aggregation and granule release (Malaver et al, 2009;Chang et al, 2011), suppressing NF-κB activation may be a way of inhibiting platelet aggregation. Several lines of evidence have confirmed that PPAR-γ and PPAR-β/-δ agonists exhibit anti-inflammatory activity by inhibiting NF-κB activation through the attenuation of IKKs and the DNAbinding activity of NF-κB in activated macrophages, smooth muscle cells and experimental periodontitis (Castrillo et al, 2000;Ikeda et al, 2000;Di Paola et al, 2011). However, the effect of PPAR-γ on NF-κB activation is controversial, and it is proposed that the described mechanisms of PPARs may be cell type and PPAR isoform specific (Ricote and Glass, 2007).…”

Section: Introductionmentioning

confidence: 99%

Antiplatelet activity of nifedipine is mediated by inhibition of NF‐κB activation caused by enhancement of PPAR‐β/‐γ activity

Shih

Lin

Ding

et al. 2014

British J Pharmacology

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BACKGROUND AND PURPOSEThe transcription factor NF-κB, stimulates platelet aggregation through a non-genomic mechanism. Nifedipine, a voltage-gated L-type calcium channel blocker, is widely used to treat hypertension. Nifedipine also displays antiplatelet activity, but the underlying mechanisms involved remain unclear. This study was designed to investigate whether the antiplatelet effects of nifedipine are mediated by regulating NF-κB-dependent responses. EXPERIMENTAL APPROACHPlatelet aggregation was measured turbidimetrically using an aggregometer. NF-κB and PPAR activation, intracellular Ca 2+ mobilization, PKCα activity, surface glycoprotein IIb/IIIa (GPIIb/IIIa) expression and platelet activation-related signalling pathways were determined in control and nifedipine-treated platelets in the presence or absence of PPAR antagonists or betulinic acid, a NF-κB activator. KEY RESULTSExposure of platelets to nifedipine significantly increased the PPAR-β/-γ activity in activated human platelets. Treatment with nifedipine reduced collagen-induced NF-κB events, including the phosphorylation of IκB kinase-β, IκBα and p65NF-κB, which were markedly attenuated by GSK0660, a PPAR-β antagonist, or GW9662, a PPAR-γ antagonist. Furthermore, the interaction of PPAR-β/-γ with NF-κB and the PPAR-β/-γ-up-regulated NO/cGMP/PKG1 cascade may contribute to inhibition of NF-κB activation by nifedipine. Suppressing PPAR-β/-γ activity or increasing NF-κB activation greatly reversed the inhibitory effect of nifedipine on collagen-induced platelet aggregation, intracellular Ca 2+ mobilization, PKCα activity and surface GPIIb/IIIa expression. CONCLUSIONS AND IMPLICATIONSPPAR-β/-γ-dependent inhibition of NF-κB activation contributes to the antiplatelet activity of nifedipine. These findings provide a novel mechanism underlying the beneficial effects of nifedipine on platelet hyperactivity-related vascular and inflammatory diseases.

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Emerging Role of PPAR-β/δin Inflammatory Process Associated to Experimental Periodontitis

Cited by 28 publications

References 17 publications

Angiotensin II/Angiotensin II Receptor Blockade Affects Osteoporosis via the AT1/AT2-Mediated cAMP-Dependent PKA Pathway

Angiotensin II/Angiotensin II Receptor Blockade Affects Osteoporosis via the AT1/AT2-Mediated cAMP-Dependent PKA Pathway

Peroxisome proliferator‐activated receptor δ inhibits Porphyromonas gingivalis lipopolysaccharide‐induced activation of matrix metalloproteinase‐2 by downregulating NADPH oxidase 4 in human gingival fibroblasts

Antiplatelet activity of nifedipine is mediated by inhibition of NF‐κB activation caused by enhancement of PPAR‐β/‐γ activity

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