scholarly journals Regulation of Regenerative Periodontal Healing by NAMPT

2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Marjan Nokhbehsaim ◽  
Sema Keser ◽  
Andreas Jäger ◽  
Søren Jepsen ◽  
James Deschner
Keyword(s):  
Periodontal Regeneration ◽  
Enamel Matrix Derivative ◽  
Regenerative Capacity ◽  
Nicotinamide Phosphoribosyltransferase ◽  
Cell Functions ◽  
Periodontal Inflammation ◽  
Pdl Cells ◽  
Increased Risk ◽  
Periodontal Healing

Periodontitis is an inflammatory disease characterized by destruction of the tooth-supporting tissues. Obese individuals have an increased risk of periodontitis, and elevated circulating levels of nicotinamide phosphoribosyltransferase (NAMPT) may be a pathomechanistic link between both diseases. Recently, increased levels of NAMPT have also been found in patients with periodontitis, irrespective of the presence of obesity. This in vitro study sought to examine the effects of NAMPT on the regenerative capacity of human periodontal ligament (PDL) cells and, thereby, periodontal healing. PDL cells treated with enamel matrix derivative (EMD), which was used to mimic regenerative healing conditions in vitro, were grown in the presence and absence of NAMPT for up to 14 d. EMD stimulated significantly (P<0.05) the expression of growth factors and their receptors, matrix molecules, osteogenesis-associated factors, and wound closure and calcium accumulation. In the presence of NAMPT, all these stimulatory effects were significantly (P<0.05) reduced. In conclusion, the beneficial effects of EMD on a number of PDL cell functions critical for periodontal regeneration are counteracted by NAMPT. Enhanced levels of NAMPT, as found in obesity and periodontal inflammation, may compromise the regenerative capacity of PDL cells and, thereby, periodontal healing in the presence of EMD.

scholarly journals Beneficial Effects of Adiponectin on Periodontal Ligament Cells under Normal and Regenerative Conditions

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Marjan Nokhbehsaim ◽  
Sema Keser ◽  
Andressa Vilas Boas Nogueira ◽  
Joni Augusto Cirelli ◽  
Søren Jepsen ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Periodontal Ligament ◽  
Periodontal Regeneration ◽  
In Vitro Study ◽  
Enamel Matrix Derivative ◽  
Periodontal Ligament Cells ◽  
Cell Functions ◽  
Diabetes And Obesity

Type 2 diabetes and obesity are increasing worldwide and linked to periodontitis, a chronic disease which is characterized by the irreversible destruction of the tooth-supporting tissues, that is, periodontium. The mechanisms underlying the association of diabetes mellitus and obesity with periodontal destruction and compromised periodontal healing are not well understood, but decreased plasma levels of adiponectin, as found in diabetic and obese individuals, might be a critical mechanistic link. The aim of this in vitro study was to examine the effects of adiponectin on periodontal ligament (PDL) cells under normal and regenerative conditions, and to study the regulation of adiponectin and its receptors in these cells. Adiponectin stimulated significantly the expression of growth factors and extracellular matrix, proliferation, and in vitro wound healing, reduced significantly the constitutive tumor necrosis factor-αexpression, and caused a significant upregulation of its own expression. The beneficial actions of enamel matrix derivative on a number of PDL cell functions critical for periodontal regeneration were partially enhanced by adiponectin. The periodontopathogenPorphyromonas gingivalisinhibited the adiponectin expression and stimulated the expression of its receptors. In conclusion, reduced levels of adiponectin, as found in type 2 diabetes and obesity, may compromise periodontal health and healing.

scholarly journals Stimulation of MMP-1 and CCL2 by NAMPT in PDL Cells

2013 ◽  
Vol 2013 ◽  
pp. 1-12 ◽  
Author(s):  
Marjan Nokhbehsaim ◽  
Sigrun Eick ◽  
Andressa Vilas Boas Nogueira ◽  
Per Hoffmann ◽  
Stefan Herms ◽  
...  
Keyword(s):  
Interleukin 1 ◽  
In Vitro Study ◽  
Serum Levels ◽  
Pathogenic Microorganisms ◽  
Nicotinamide Phosphoribosyltransferase ◽  
Pdl Cells ◽  
Increased Risk ◽  
Circulating Levels ◽  
Stimulation Of

Periodontitis is an inflammatory disease caused by pathogenic microorganisms and characterized by the destruction of the periodontium. Obese individuals have an increased risk of periodontitis, and elevated circulating levels of adipokines, such as nicotinamide phosphoribosyltransferase (NAMPT), may be a pathomechanistic link between both diseases. The aim of this in vitro study was to examine the regulation of periodontal ligament (PDL) cells by NAMPT and its production under inflammatory and infectious conditions. NAMPT caused a significant upregulation of 9 genes and downregulation of 3 genes, as analyzed by microarray analysis. Eight of these genes could be confirmed by real-time PCR: NAMPT induced a significant upregulation of EGR1, MMP-1, SYT7, ITPKA, CCL2, NTM, IGF2BP3, and NRP1. NAMPT also increased significantly the MMP-1 and CCL2 protein synthesis. NAMPT was significantly induced by interleukin-1βand the periodontal microorganismP. gingivalis. NAMPT may contribute to periodontitis through upregulation of MMP-1 and CCL2 in PDL cells. Increased NAMPT levels, as found in obesity, may therefore represent a mechanism whereby obesity could confer an increased risk of periodontitis. Furthermore, microbial and inflammatory signals may enhance the NAMPT synthesis in PDL cells and thereby contribute to the increased gingival and serum levels of this adipokine, as found in periodontitis.

scholarly journals Regulation of Periodontal Ligament Cell Functions by Interleukin-1β

1998 ◽  
Vol 66 (3) ◽  
pp. 932-937 ◽  
Author(s):  
Sudha Agarwal ◽  
Charu S. Chandra ◽  
Nicholas P. Piesco ◽  
Herman H. Langkamp ◽  
Lathe Bowen ◽  
...  
Keyword(s):  
Proinflammatory Cytokines ◽  
Periodontal Ligament ◽  
Transforming Growth Factor ◽  
Disease Process ◽  
Interleukin 1Β ◽  
Phenotypic Change ◽  
Phenotypic Changes ◽  
Cell Functions ◽  
Periodontal Inflammation ◽  
Pdl Cells

ABSTRACT Periodontal ligament (PDL) cells maintain the attachment of the tooth to alveolar bone. These cells reside at a site in which they are challenged frequently by bacterial products and proinflammatory cytokines, such as interleukin-1β (IL-1β), during infections. In our initial studies we observed that IL-1β down-regulates the osteoblast-like characteristics of PDL cells in vitro. Therefore, we examined the functional significance of the loss of the PDL cell’s osteoblast-like characteristics during inflammation. In this report we show that, during inflammation, IL-1β can modulate the phenotypic characteristics of PDL cells to a more functionally significant lipopolysaccharide (LPS)-responsive phenotype. In a healthy periodontium PDL cells exhibit an osteoblast-like phenotype and are unresponsive to gram-negative bacterial LPS. Treatment of PDL cells with IL-1β inhibits the expression of their osteoblast-like characteristics, as assessed by the failure to express transforming growth factor β1 (TGF-β1) and proteins associated with mineralization, such as alkaline phosphatase and osteocalcin. As a consequence of this IL-1β-induced phenotypic change, PDL cells become responsive to LPS and synthesize proinflammatory cytokines. The IL-1β-induced phenotypic changes in PDL cells were transient, as removal of IL-1β from PDL cell cultures resulted in reacquisition of their osteoblast-like characteristics and lack of LPS responsiveness. The IL-1β-induced phenotypic changes occurred at concentrations that are frequently observed in tissue exudates during periodontal inflammation (0.05 to 5 ng/ml). The results suggest that, during inflammation in vivo, IL-1β may modulate PDL cell functions, allowing PDL cells to participate directly in the disease process by assuming LPS responsiveness at the expense of their normal structural properties and functions.

scholarly journals Contribution of Statins towards Periodontal Treatment: A Review

2019 ◽  
Vol 2019 ◽  
pp. 1-33 ◽  
Author(s):  
Catherine Petit ◽  
Fareeha Batool ◽  
Isaac Maximiliano Bugueno ◽  
Pascale Schwinté ◽  
Nadia Benkirane-Jessel ◽  
...  
Keyword(s):  
Host Response ◽  
Periodontal Therapy ◽  
Periodontal Treatment ◽  
Bacterial Clearance ◽  
Systemic Delivery ◽  
Periodontal Inflammation ◽  
Immune Mediated ◽  
Periodontal Healing

The pleiotropic effects of statins have been evaluated to assess their potential benefit in the treatment of various inflammatory and immune-mediated diseases including periodontitis. Herein, the adjunctive use of statins in periodontal therapy in vitro, in vivo, and in clinical trials was reviewed. Statins act through several pathways to modulate inflammation, immune response, bone metabolism, and bacterial clearance. They control periodontal inflammation through inhibition of proinflammatory cytokines and promotion of anti-inflammatory and/or proresolution molecule release, mainly, through the ERK, MAPK, PI3-Akt, and NF-κB pathways. Moreover, they are able to modulate the host response activated by bacterial challenge, to prevent inflammation-mediated bone resorption and to promote bone formation. Furthermore, they reduce bacterial growth, disrupt bacterial membrane stability, and increase bacterial clearance, thus averting the exacerbation of infection. Local statin delivery as adjunct to both nonsurgical and surgical periodontal therapies results in better periodontal treatment outcomes compared to systemic delivery. Moreover, combination of statin therapy with other regenerative agents improves periodontal healing response. Therefore, statins could be proposed as a potential adjuvant to periodontal therapy. However, optimization of the combination of their dose, type, and carrier could be instrumental in achieving the best treatment response.

scholarly journals Leptin Effects on the Regenerative Capacity of Human Periodontal Cells

2014 ◽  
Vol 2014 ◽  
pp. 1-13 ◽  
Author(s):  
Marjan Nokhbehsaim ◽  
Sema Keser ◽  
Andressa Vilas Boas Nogueira ◽  
Andreas Jäger ◽  
Søren Jepsen ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Periodontal Ligament ◽  
Bioactive Molecules ◽  
Regenerative Capacity ◽  
Endocrine Organ ◽  
Pdl Cells ◽  
Underlying Mechanisms ◽  
The Impact ◽  
Periodontal Healing ◽  
Local Expression

Obesity is increasing throughout the globe and characterized by excess adipose tissue, which represents a complex endocrine organ. Adipose tissue secrets bioactive molecules called adipokines, which act at endocrine, paracrine, and autocrine levels. Obesity has recently been shown to be associated with periodontitis, a disease characterized by the irreversible destruction of the tooth-supporting tissues, that is, periodontium, and also with compromised periodontal healing. Although the underlying mechanisms for these associations are not clear yet, increased levels of proinflammatory adipokines, such as leptin, as found in obese individuals, might be a critical pathomechanistic link. The objective of this study was to examine the impact of leptin on the regenerative capacity of human periodontal ligament (PDL) cells and also to study the local leptin production by these cells. Leptin caused a significant downregulation of growth (TGFβ1, and VEGFA) and transcription (RUNX2) factors as well as matrix molecules (collagen, and periostin) and inhibited SMAD signaling under regenerative conditions. Moreover, the local expression of leptin and its full-length receptor was significantly downregulated by inflammatory, microbial, and biomechanical signals. This study demonstrates that the hormone leptin negatively interferes with the regenerative capacity of PDL cells, suggesting leptin as a pathomechanistic link between obesity and compromised periodontal healing.

scholarly journals Hypoxia andP. gingivalisSynergistically Induce HIF-1 and NF-κB Activation in PDL Cells and Periodontal Diseases

2015 ◽  
Vol 2015 ◽  
pp. 1-12 ◽  
Author(s):  
L. Gölz ◽  
S. Memmert ◽  
B. Rath-Deschner ◽  
A. Jäger ◽  
T. Appel ◽  
...  
Keyword(s):  
Target Genes ◽  
Periodontal Diseases ◽  
Anaerobic Bacteria ◽  
Periodontal Pathogen ◽  
Tissue Samples ◽  
Periodontal Tissues ◽  
Periodontal Inflammation ◽  
Matrix Metalloproteinase 1 ◽  
Pdl Cells

Periodontitis is characterized by deep periodontal pockets favoring the proliferation of anaerobic bacteria likePorphyromonas gingivalis(P. gingivalis), a periodontal pathogen frequently observed in patients suffering from periodontal inflammation. Therefore, the aim of the present study was to investigate the signaling pathways activated by lipopolysaccharide (LPS) ofP. gingivalis(LPS-PG) and hypoxia in periodontal ligament (PDL) cells. The relevant transcription factors nuclear factor-kappa B (NF-κB) and hypoxia inducible factor-1 (HIF-1) were determined. In addition, we analyzed the expression of interleukin- (IL-) 1β, matrix metalloproteinase-1 (MMP-1), and vascular endothelial growth factor (VEGF) in PDL cells on mRNA and protein level. This was accomplished by immunohistochemistry of healthy and inflamed periodontal tissues. We detected time-dependent additive effects of LPS-PG and hypoxia on NF-κB and HIF-1αactivation in PDL cells followed by an upregulation of IL-1β, MMP-1, and VEGF expression. Immunohistochemistry performed on tissue samples of gingivitis and periodontitis displayed an increase of NF-κB, HIF-1, and VEGF immunoreactivity in accordance with disease progression validating the importance of thein vitroresults. To conclude, the present study underlines the significance of NF-κB and HIF-1αand their target genes VEGF, IL-1β, and MMP-1 inP. gingivalisand hypoxia induced periodontal inflammatory processes.

Decellularized bone extracellular matrix in skeletal tissue engineering

2020 ◽  
Vol 48 (3) ◽  
pp. 755-764
Author(s):  
Benjamin B. Rothrauff ◽  
Rocky S. Tuan
Keyword(s):  
Tissue Engineering ◽  
Bone Regeneration ◽  
Tissue Regeneration ◽  
Animal Studies ◽  
Tumor Resection ◽  
Regenerative Capacity ◽  
Skeletal Tissue ◽  
Large Bone

Bone possesses an intrinsic regenerative capacity, which can be compromised by aging, disease, trauma, and iatrogenesis (e.g. tumor resection, pharmacological). At present, autografts and allografts are the principal biological treatments available to replace large bone segments, but both entail several limitations that reduce wider use and consistent success. The use of decellularized extracellular matrices (ECM), often derived from xenogeneic sources, has been shown to favorably influence the immune response to injury and promote site-appropriate tissue regeneration. Decellularized bone ECM (dbECM), utilized in several forms — whole organ, particles, hydrogels — has shown promise in both in vitro and in vivo animal studies to promote osteogenic differentiation of stem/progenitor cells and enhance bone regeneration. However, dbECM has yet to be investigated in clinical studies, which are needed to determine the relative efficacy of this emerging biomaterial as compared with established treatments. This mini-review highlights the recent exploration of dbECM as a biomaterial for skeletal tissue engineering and considers modifications on its future use to more consistently promote bone regeneration.

Assays for Phospholipid-Dependent Formation of Thrombin and Xa: A Potential Method for Quantifying Lupus Anticoagulant Activity

1991 ◽  
Vol 66 (04) ◽  
pp. 453-458 ◽  
Author(s):  
John T Brandt
Keyword(s):  
Specific Activity ◽  
Anticoagulant Activity ◽  
Factor Xa ◽  
Clinical Importance ◽  
Potential Method ◽  
Quantitative Expression ◽  
Increased Risk ◽  
Apparent Association

SummaryLupus anticoagulants (LAs) are antibodies which interfere with phospholipid-dependent procoagulant reactions. Their clinical importance is due to their apparent association with an increased risk of thrombo-embolic disease. To date there have been few assays for quantifying the specific activity of these antibodies in vitro and this has hampered attempts to purify and characterize these antibodies. Methods for determining phospholipid-dependent generation of thrombin and factor Xa are described. Isolated IgG fractions from 7 of 9 patients with LAs were found to reproducibly inhibit enzyme generation in these assay systems, permitting quantitative expression of inhibitor activity. Different patterns of inhibitory activity, based on the relative inhibition of thrombin and factor Xa generation, were found, further substantiating the known heterogeneity of these antibodies. These systems may prove helpful in further purification and characterization of LAs.

Defibrotide Inhibits Platelet Activation by Cathepsin G Released From Stimulated Polymorphonuclear Leukocytes

1992 ◽  
Vol 67 (06) ◽  
pp. 660-664 ◽  
Author(s):  
Virgilio Evangelista ◽  
Paola Piccardoni ◽  
Giovanni de Gaetano ◽  
Chiara Cerletti
Keyword(s):  
Platelet Activation ◽  
Polymorphonuclear Leukocytes ◽  
Direct Interaction ◽  
Cathepsin G ◽  
In Vivo Test ◽  
Cell Functions ◽  
Test Models ◽  
Antithrombotic Effects

SummaryDefibrotide is a polydeoxyribonucleotide with antithrombotic effects in experimental animal models. Most of the actions of this drug have been observed in in vivo test models but no effects have been reported in in vitro systems. In this paper we demonstrate that defibrotide interferes with polymorphonuclear leukocyte-induced human platelet activation in vitro. This effect was not related to any direct interaction with polymorphonuclear leukocytes or platelets, but was due to the inhibition of cathepsin G, the main biochemical mediator of this cell-cell cooperation. Since cathepsin G not only induces platelet activation but also affects some endothelial cell functions, the anticathepsin G activity of defibrotide could help to explain the antithrombotic effect of this drug.

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