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  • 1
    In: International Endodontic Journal, Wiley, Vol. 56, No. 2 ( 2023-02), p. 193-202
    Abstract: To evaluate the expression and function of the nod‐like receptor pyrin domain containing 3 (NLRP3) inflammasome in caries induced pulpitis. Methodology NLRP3 expression was determined with immunohistochemistry in the dental pulp and qPCR in dental pulp cells (DPCs). THP‐1 macrophages expressing the apoptosis‐related speck‐like protein (ASC) and green fluorescent protein (GFP) fusion protein were used to assess NLRP3 inflammasome activation by live cell imaging, following treatment with lipopolysaccharide (LPS) and lipoteichoic acid (LTA). Caspase I inhibitor was used to confirm inflammasome activation. An ex‐vivo pulpitis model in which the DPCs were co‐cultured with THP‐1 macrophages was used to study the effect of the NLRP3 inflammasome inhibitor (MCC950), and cytokines were measured using ELISA and multiplex array. Data were analysed using the t‐test or anova followed by a Bonferroni post hoc test with the level of significance set at p  ≤ .05. Results NLRP3 inflammasome was differentially expressed in dental pulp of sound and carious teeth. Treatment of DPCs with LTA significantly upregulates NLRP3 and IL‐1 β‐expression ( p   〈  .05) and in induces more ASC specks formation compared to LPS. IL‐β release in response to LTA treatment is significantly reduced with Caspase I inhibitor suggesting inflammasome dependent mechanism ( p   〈  .01). NLRP3‐specific inhibitor, MCC950, significantly reduced IL‐1β and IL‐6 in an ex‐vivo pulpitis model ( p   〈  .01) but had no effect on IL‐8 or matrix metalloproteinase‐9 (MMP‐9). Conclusions Expression and upregulation of NLRP3 inflammasome with caries and LTA treatment suggest a role in caries‐induced pulpitis. NLRP3 inhibitor attenuated the release of selective inflammatory cytokines and could be a potential treatment target that merit further investigation.
    Type of Medium: Online Resource
    ISSN: 0143-2885 , 1365-2591
    URL: Issue
    RVK:
    Language: English
    Publisher: Wiley
    Publication Date: 2023
    detail.hit.zdb_id: 2020354-8
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  • 2
    Online Resource
    Online Resource
    Wiley ; 2008
    In:  Journal of Biomedical Materials Research Part B: Applied Biomaterials Vol. 85B, No. 1 ( 2008-04), p. 180-187
    In: Journal of Biomedical Materials Research Part B: Applied Biomaterials, Wiley, Vol. 85B, No. 1 ( 2008-04), p. 180-187
    Abstract: In a previous work, based on an in vitro entire tooth culture model of human immature third molars, we demonstrated that perivascular progenitor cells can proliferate and migrate to the injury site after pulp exposure. In this work, we investigated the differentiation of cells after direct capping with biomaterials classically used in restorative dentistry. Histological staining after direct pulp capping with Calcium Hydroxide XR® or MTA revealed early and progressive mineralized foci formation containing BrdU‐labeled sequestered cells. The molecular characterization of the matrix and the sequestered cells by immunohistochemistry (Collagene type I, Dentin sialoprotein, and Nestin) clearly demonstrates that these areas share common characteristics of the mineralized matrix of reparative dentin formed by odontoblast‐like cells. This reproduces some features of the pulp responses after applying these materials in vivo and demonstrates that the entire tooth culture model reproduces a part of the early steps of dentin regeneration in vivo. Its future development may be useful in studying the effects of biomaterials on this process. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2008
    Type of Medium: Online Resource
    ISSN: 1552-4973 , 1552-4981
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2008
    detail.hit.zdb_id: 2130917-6
    SSG: 12
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  • 3
    Online Resource
    Online Resource
    Wiley ; 2002
    In:  Journal of Biomedical Materials Research Vol. 63, No. 4 ( 2002-01), p. 418-423
    In: Journal of Biomedical Materials Research, Wiley, Vol. 63, No. 4 ( 2002-01), p. 418-423
    Abstract: Odontoblasts are highly differentiated postmitotic cells, which under pathological conditions such as carious lesions and dental injuries may degenerate and be replaced by other pulp cells. A recent work showed that this physiological event can be reproduced in an in vitro assay system. The purpose of the present study was to evaluate the effects of resinous monomers on odontoblast differentiation in vitro. Pulp cores from extracted human third molars were cultured with β‐glycerophosphate (2 mM) and used to evaluate the effects of TEGDMA, HEMA, UDMA, and Bis‐GMA on the differentiation of pulp fibroblasts into odontoblasts. The effect of the monomers was studied by evaluating the expression of several odontoblast specific genes. In the absence of monomers, mineral nodule formation was observed. Pulp cells contributing to the nodule formation synthesized type I collagen, osteonectin, and dentin sialoprotein (DSP). In addition, Fourier transform infrared microspectroscopy showed that the mineral and organic composition of the nodules were characteristic of dentin. When the monomers were added at nontoxic concentrations, the effects of HEMA and Bis‐GMA were more evident than that of TEGDMA and UDMA on collagen 1, osteonectin, and DSP expression. However, all monomers significantly decreased DSP expression and completely inhibited the mineral nodule formation. © 2002 Wiley Periodicals, Inc. J Biomed Mater Res (Appl Biomater) 63: 418–423, 2002
    Type of Medium: Online Resource
    ISSN: 0021-9304 , 1097-4636
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2002
    detail.hit.zdb_id: 2176174-7
    SSG: 12
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  • 4
    Online Resource
    Online Resource
    Wiley ; 2013
    In:  Endodontic Topics Vol. 28, No. 1 ( 2013-03), p. 61-89
    In: Endodontic Topics, Wiley, Vol. 28, No. 1 ( 2013-03), p. 61-89
    Abstract: Understanding dentinogenesis and pulp regeneration during physiological and pathological conditions represents a real challenge in the provision of a suitable treatment that ideally leads to the induction of the pulp regenerative potential. This paper focusses on the early steps of dentin–pulp regeneration that appear to be critical after pulp capping procedures. Different models are described in this paper where the interactions between different cell types in vitro illustrate their role in maintaining pulpal homeostasis. After traumatic injuries, the cells modify the local pulpal microenvironment by secreting growth factors that orchestrate and induce the processes required for dentin–pulp regeneration. Applying dental materials onto the injured pulp modifies this local microenvironment and affects the potential for pulpal regeneration. The paper also describes the added value of developing an entire human tooth culture model for understanding these early steps and discusses the interest of its use in evaluating newly developed pulp capping materials through the example of B iodentine TM , developed as a dentin substitute. The growth factors sustained release simulating the local microenvironment is also discussed. Simulating the pulp local environment with a continuous growth factors release is also a basic requirement for establishing future pulp tissue engineering.
    Type of Medium: Online Resource
    ISSN: 1601-1538 , 1601-1546
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2013
    detail.hit.zdb_id: 2082044-6
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  • 5
    In: The FASEB Journal, Wiley, Vol. 35, No. 5 ( 2021-05)
    Type of Medium: Online Resource
    ISSN: 0892-6638 , 1530-6860
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2021
    detail.hit.zdb_id: 1468876-1
    SSG: 12
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  • 6
    Online Resource
    Online Resource
    Wiley ; 2013
    In:  Endodontic Topics Vol. 28, No. 1 ( 2013-03), p. 118-118
    In: Endodontic Topics, Wiley, Vol. 28, No. 1 ( 2013-03), p. 118-118
    Type of Medium: Online Resource
    ISSN: 1601-1538 , 1601-1546
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2013
    detail.hit.zdb_id: 2082044-6
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  • 7
    In: International Endodontic Journal, Wiley, Vol. 54, No. 9 ( 2021-09), p. 1571-1580
    Abstract: To create an irreversible pulpitis gene signature from microarray data of healthy and inflamed dental pulps, followed by a bioinformatics approach using connectivity mapping to identify therapeutic compounds that could potentially treat pulpitis. Methodology The Gene Expression Omnibus (GEO) database, an international public repository of genomics data sets, was searched for human microarray datasets assessing pulpitis. An irreversible pulpitis gene expression signature was generated by differential expression analysis. The statistically significant connectivity map (ssCMap) method was used to identify compounds with a highly correlating gene expression pattern. qPCR was used to validate novel pulpitis genes. An ex vivo pulpitis model was used to test the effects of the compounds identified, and the level of inflammatory cytokines was measured with qPCR, ELISA and multiplex array. Means were compared using the t‐test or ANOVA with the level of significance set at p  ≤ .05. Results Pulpitis gene signatures were created using differential gene expression analysis at cutoff points p  = .0001 and .000018. Top upregulated genes were selected as potential pulpitis biomarkers. Among these, IL8, IL6 and MMP9 were previously identified as pulpitis biomarkers. Novel upregulated genes, chemokine (C‐C motif) ligand 21 (CCL21), metallothionein 1H (MT1H) and aquaporin 9 (AQP9) were validated in the pulp tissue of teeth clinically diagnosed with irreversible pulpitis using qPCR. ssCMap analysis identified fluvastatin (Statin) and dequalinium chloride (Quaternary ammonium) as compounds with the strongest correlation to the gene signatures ( p  = .0001). Fluvastatin reduced IL8, IL6, CCL21, AQP9 ( p  〈  .001) and MMP9 ( p  〈  .05) in the ex vivo pulpitis model, while dequalinium chloride reduced AQP9 ( p  〈  .001) but had no significant effect on the other biomarkers. Conclusions AQP9, MT1H and CCL21 were identified and validated as novel biomarkers for pulpitis. Fluvastatin and dequalinium chloride identified by the ssCMap as potential therapeutics for pulpitis reduced selected pulpitis biomarkers in an ex vivo pulpitis model. In vivo testing of these licenced drugs is warranted.
    Type of Medium: Online Resource
    ISSN: 0143-2885 , 1365-2591
    URL: Issue
    RVK:
    Language: English
    Publisher: Wiley
    Publication Date: 2021
    detail.hit.zdb_id: 2020354-8
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