Abstract：
:Histone deacetylases (HDACs) are important regulators of gene expression that are aberrantly regulated in several inflammatory and infectious diseases. HDAC inhibitors (HDACi) suppress inflammatory activation of various cell types through epigenetic and non-epigenetic mechanisms, and ameliorate pathology in a mouse model of periodontitis. Activation of gingival fibroblasts (GFs) significantly contributes to the development of periodontitis and the anaerobic bacterium Porphyromonas gingivalis plays a key role in driving chronic inflammation. Here, we analyzed the role of HDACs in inflammatory responses of GFs. Pan-HDACi suberoylanilide hydroxamic acid (SAHA) and/or ITF2357 (givinostat) significantly reduced TNFα- and P. gingivalis-inducible expression and/or production of a cluster of inflammatory mediators in healthy donor GFs (IL1B, CCL2, CCL5, CXCL10, COX2, and MMP3) without affecting cell viability. Selective inhibition of HDAC3/6, but not specific HDAC1, HDAC6, or HDAC8 inhibition, reproduced the suppressive effects of pan-HDACi on the inflammatory gene expression profile induced by TNFα and P. gingivalis, suggesting a critical role for HDAC3 in GF inflammatory activation. Consistently, silencing of HDAC3 expression with siRNA largely recapitulated the effects of HDAC3/6i on mRNA levels of inflammatory mediators in P. gingivalis-infected GFs. In contrast, P. gingivalis internalization and intracellular survival in GFs remained unaffected by HDACi. Activation of mitogen-activated protein kinases and NFκB signaling was unaffected by global or HDAC3/6-selective HDACi, and new protein synthesis was not required for gene suppression by HDACi. Finally, pan-HDACi and HDAC3/6i suppressed P. gingivalis-induced expression of IL1B, CCL2, CCL5, CXCL10, MMP1, and MMP3 in GFs from patients with periodontitis. Our results identify HDAC3 as an important regulator of inflammatory gene expression in GFs and suggest that therapeutic targeting of HDAC activity, in particular HDAC3, may be clinically beneficial in suppressing inflammation in periodontal disease.
journal_name
J Dent Resjournal_title
Journal of dental researchauthors
Lagosz KB,Bysiek A,Macina JM,Bereta GP,Kantorowicz M,Lipska W,Sochalska M,Gawron K,Kaczmarzyk T,Chomyszyn-Gajewska M,Fossati G,Potempa J,Grabiec AMdoi
10.1177/0022034519885088subject
Has Abstractpub_date
2020-01-01 00:00:00pages
98-106issue
1eissn
0022-0345issn
1544-0591journal_volume
99pub_type
杂志文章abstract：:The purpose of this study was to determine the role of saliva-derived biomarkers and periodontal pathogens during periodontal disease progression (PDP). One hundred human participants were recruited into a 12-month investigation. They were seen bi-monthly for saliva and clinical measures and bi-annually for subtractio...
journal_title：Journal of dental research
pub_type： 临床试验,杂志文章
doi：10.1177/0022034511399908
更新日期：2011-06-01 00:00:00
abstract：:The major phosphoprotein in dentin is the aspartic acid and serine-rich protein called dentin phosphophoryn (DPP). DPP appears to be synthesized as a part of a larger compound protein, dentin sialophosphoprotein (DSPP). DSPP has never been isolated or detected in dentin extracts. It is now evident that DSPP is a chime...
journal_title：Journal of dental research
pub_type： 杂志文章
doi：10.1177/0022034513516631
更新日期：2014-02-01 00:00:00
abstract：:Tumor progression is often associated with altered glycosylation of the cell-surface proteins and lipids. The peripheral part of these cell-surface glycoconjugates often carries carbohydrate structures related to the ABO and Lewis blood-group antigens. The expression of histo-blood-group antigens in normal human tissu...
journal_title：Journal of dental research
pub_type： 杂志文章,评审
doi：10.1177/154405910508400103
更新日期：2005-01-01 00:00:00
abstract：:An analysis of the relationship between creep and microstructural characteristics of several gamma2-containing amalgams showed the grain size of the Ag-Hg phase (gamma1) to be a predominant factor influencing creep. When gamma1 grain size is increased, creep is reduced. ...
journal_title：Journal of dental research
pub_type： 杂志文章
doi：10.1177/00220345770560121401
更新日期：1977-12-01 00:00:00
abstract：:Because of the greater sensitivity of commonly used dental films near 40 kv and the inherently greater contrast between bone and other oral tissues that is achieved at lower energies than those conventionally used, a considerable reduction of radiation exposure can be obtained by the use of those quasimonochromatic ph...
journal_title：Journal of dental research
pub_type： 杂志文章
doi：10.1177/00220345760550010801
更新日期：1976-01-01 00:00:00
abstract：:The term "artificial intelligence" (AI) refers to the idea of machines being capable of performing human tasks. A subdomain of AI is machine learning (ML), which "learns" intrinsic statistical patterns in data to eventually cast predictions on unseen data. Deep learning is a ML technique using multi-layer mathematical...
journal_title：Journal of dental research
pub_type： 杂志文章
doi：10.1177/0022034520915714
更新日期：2020-07-01 00:00:00
abstract：:Restriction endonuclease analysis (REA) was performed on the total cellular DNA from each of 396 strains of mutans streptococci (1) to determine its potential usefulness for the study of transmission of the organism and (2) to document the proportions and variety of strains harbored by members of a small group of fami...
journal_title：Journal of dental research
pub_type： 杂志文章
doi：10.1177/00220345890680070401
更新日期：1989-07-01 00:00:00
abstract：:Various etching methods are examined with respect to their ability to induce the surface nucleation and growth of fluorapatite from solutions of low, sustained supersaturation with respect to hydroxyapatite and fluorapatite. The constant composition kinetics method enables the rates of remineralization to be precisely...
journal_title：Journal of dental research
pub_type： 杂志文章
doi：10.1177/00220345820610091301
更新日期：1982-09-01 00:00:00
abstract：:The composition of the degradable glasses used in commercial dental glass-ionomer cements determines their leaching behavior and hence the properties of the cement. The objective of the present study was to assess if the composition and leaching in acetic acid solutions are reflected in the x-ray diffraction character...
journal_title：Journal of dental research
pub_type： 杂志文章
doi：10.1177/00220345010800081601
更新日期：2001-08-01 00:00:00
abstract：:In this study, we investigated whether selective activation of nociceptive primary afferent fibers by capsaicin would induce modulations on tooth-pulp-evoked sensory or inhibitory masseter reflex responses in healthy human subjects. The contribution of central N-methyl-D-aspartate (NMDA) receptor mechanisms in capsaic...
journal_title：Journal of dental research
pub_type： 杂志文章
doi：10.1177/00220345970760090801
更新日期：1997-09-01 00:00:00
abstract：:Previous studies suggest that salivary and pulp-derived host enzymes, matrix metalloproteinases (MMPs), may be involved in dentin caries pathogenesis. To study the inhibition of acid-activated human salivary MMPs by non-antimicrobial chemically modified tetracyclines (CMTs), we used a functional activity assay with 12...
journal_title：Journal of dental research
pub_type： 杂志文章
doi：10.1177/00220345010800061301
更新日期：2001-06-01 00:00:00
abstract：:Calcitonin gene-related peptide (CGRP) plays a crucial role in the modulation of orofacial pain, and we hypothesized that CGRP mediated a neuron-glia crosstalk in orofacial pain. The objective of this study was to elucidate the mechanisms whereby CGRP mediated trigeminal neuron-glia crosstalk in modulating orofacial p...
journal_title：Journal of dental research
pub_type： 杂志文章
doi：10.1177/0022034520950296
更新日期：2021-01-01 00:00:00
abstract：:We have investigated the role of the activation of nuclear poly(ADP-ribose) polymerase (PARP) enzyme, a mediator of downstream nitric oxide toxicity, using a combined approach of pharmacological inhibition and genetic disruption in a ligature-induced-periodontitis model in rats and mice. Immunohistochemical analysis r...
journal_title：Journal of dental research
pub_type： 杂志文章
doi：10.1177/154405910308201210
更新日期：2003-12-01 00:00:00
abstract：:A detailed understanding of the complexity of root canal systems is imperative to ensure successful root canal preparation. The aim of this study was to evaluate the potential and accuracy of a three-dimensional, non-destructive technique for detailing root canal geometry by means of high-resolution tomography. The an...
journal_title：Journal of dental research
pub_type： 杂志文章
doi：10.1177/00220345000790060901
更新日期：2000-06-01 00:00:00
abstract：:Not only are teeth essential for mastication, but also missing teeth are considered a social handicap due to speech and aesthetic problems, with a resulting high impact on emotional well-being. Several treatment procedures are currently available for tooth replacement with mostly inert prosthetic materials and implant...
journal_title：Journal of dental research
pub_type： 杂志文章,评审
doi：10.1177/0022034509355440
更新日期：2010-02-01 00:00:00
abstract：:Teeth develop through distinct morphological stages. At the cap stage, a compactly clustered and concentrically arranged cell mass, the enamel knot, appears at the tip of the enamel organ. Cells in this knot express sets of key molecules, and as such have been proposed to act as a signaling center directing tooth morp...
journal_title：Journal of dental research
pub_type： 杂志文章
doi：10.1177/0022034514525784
更新日期：2014-05-01 00:00:00
abstract：:Current knowledge regarding the sensitivity of the teeth to forces is based on psychophysical experiments that measured touch detection thresholds under static jaw conditions. It is not known whether jaw movements alter the perception of forces applied to the teeth, but, based on limb movement studies, it is hypothesi...
journal_title：Journal of dental research
pub_type： 杂志文章
doi：10.1177/0022034510363101
更新日期：2010-04-01 00:00:00
abstract：:The aim of the present study was to describe the patterns of dental fluorosis in the primary and the permanent dentition of children born and reared in two different fluoridated areas, one in which powdered milk suspended in tap water was commonly used (Narssaq, Greenland: 1.1 ppm fluoride in the water) and one in whi...
journal_title：Journal of dental research
pub_type： 杂志文章
doi：10.1177/00220345880670050501
更新日期：1988-05-01 00:00:00
abstract：:The proton probe has been used to map F concentration changes in the enamel of 15 teeth showing clinical evidence of caries. Thin sections through the lesions were microradiographed and measurements made of the surface zone (radiodense) and body (radiolucent) areas. Each section was then scanned with a focused beam of...
journal_title：Journal of dental research
pub_type： 杂志文章
doi：10.1177/00220345950740111001
更新日期：1995-11-01 00:00:00
abstract：:The diagnosis of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection relies on the detection of viral RNA by real-time reverse transcription polymerase chain reaction (rRT-PCR) performed with respiratory specimens, especially nasopharyngeal swabs. However, this procedure requires specialized medical...
journal_title：Journal of dental research
pub_type： 杂志文章
doi：10.1177/0022034520969670
更新日期：2021-02-01 00:00:00
abstract：:A gravity sintering fabrication technique has been developed for producing Co-Cr-Mo alloy dental implants having a porous coating on the root portion. This process allows for control of pore structure enabling ingrowth of either bone or fibrous tissue. The microstructure and mechanical properties of these materials ha...
journal_title：Journal of dental research
pub_type： 杂志文章
doi：10.1177/00220345770560050501
更新日期：1977-05-01 00:00:00
abstract：:The eventual outcome of dental caries is determined by the dynamic balance between pathological factors that lead to demineralization and protective factors that lead to remineralization. Pathological factors include acidogenic bacteria, inhibition of salivary function, and frequency of ingestion of fermentable carboh...
journal_title：Journal of dental research
pub_type： 杂志文章,评审
doi：10.1177/154405910408301s08
更新日期：2004-01-01 00:00:00
abstract：:A three-month study of the chemistry of the water erosion of two forms of ASPA cement has been made. The effect of varying cement consistency and cure time was investigated. The results are discussed in terms of the known chemistry and structure of the cement. The erosion behavior is compared to that of silicate, sili...
journal_title：Journal of dental research
pub_type： 杂志文章
doi：10.1177/00220345760550060501
更新日期：1976-11-01 00:00:00
abstract：:Previous studies of tooth size in twins and their families have suggested a high degree of genetic control, although there have been difficulties separating the various genetic and environmental effects. A genetic analysis of variation in crown size of the permanent incisors of South Australian twins was carried out, ...
journal_title：Journal of dental research
pub_type： 杂志文章
doi：10.1177/00220345950740071101
更新日期：1995-07-01 00:00:00
abstract：:Heads of Swiss-Webster mouse fetuses of four ages spanning days 12-13 of gestation, were partially dissected by removing the brain (B), tongue (T) and mandible (M) alone or in combination (BT, BM, BTM). Preparations were suspended in a gassed, circulating culture system such that palatal closure must take place agains...
journal_title：Journal of dental research
pub_type： 杂志文章
doi：10.1177/00220345780570024401
更新日期：1978-02-01 00:00:00
abstract：:The effect of toothbrushes on soft tissue abrasion was measured using hamster cheek pouch tissue brushed mechanically for various intervals. The detection of protein removed during brushing was used as an index of tissue abrasion. The method was found to be sensitive in detecting the effects of brush load, number of s...
journal_title：Journal of dental research
pub_type： 杂志文章
doi：10.1177/00220345770560070301
更新日期：1977-07-01 00:00:00
abstract：:The histopathologic status of gingival tissue was assessed according to the criteria of Page and Schroeder.(5) Rhodamine-labeled bacteria were used to assess the antigenic specificity of plasma cells in the tissue. Examination of tissue sections revealed that 31.6% of plasma cells in the advanced lesions bound the lab...
journal_title：Journal of dental research
pub_type： 杂志文章
doi：10.1177/0022034580059S213
更新日期：1980-11-01 00:00:00
abstract：:Schoolchildren residing in a fluoride-deficient area were provided either a sodium fluoride (0.1% F) or a nonfluoride dentifrice for home use. About half the children provided each type of dentifrice were also given an initial prophylaxis. Combining the data with regard to the type of dentifrice indicated that the sod...
journal_title：Journal of dental research
pub_type： 临床试验,杂志文章
doi：10.1177/00220345750540013601
更新日期：1975-01-01 00:00:00
abstract：:Although it is known that diabetes impairs oral wound healing, relatively little is known about the cellular parameters affected, particularly in connective tissue. This study investigated the hypothesis that diabetes impairs connective tissue formation in healing gingiva, and that impaired healing is associated with ...
journal_title：Journal of dental research
pub_type： 杂志文章
doi：10.1177/0022034510362960
更新日期：2010-06-01 00:00:00
abstract：:Evaluation of long-term mechanical behavior of new types of restorations in clinical trials is time-consuming. A partial alternative can be found in experimental fatigue-testing, which simulates accelerated mechanical deterioration. The aim of this study was to determine the feasibility of using fatigue-testing of a c...
journal_title：Journal of dental research
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1177/00220345920710050301
更新日期：1992-05-01 00:00:00
