Elsevier

Journal of Endodontics

Volume 43, Issue 7, July 2017, Pages 1033-1051
Journal of Endodontics

Review Article
Pulp Inflammation Diagnosis from Clinical to Inflammatory Mediators: A Systematic Review

https://doi.org/10.1016/j.joen.2017.02.009Get rights and content

Highlights

  • Clinical evaluation does not accurately diagnose pulp inflammation severity.

  • Biomarker quantification may aid in the distinction between reversible and irreversible pulpitis.

  • IL-8, MMP-9, TNF-α, and RAGE expression increased in the inflamed dental pulp.

Abstract

Introduction

Similar to other tissues, the dental pulp mounts an inflammatory reaction as a way to eliminate pathogens and stimulate repair. Pulp inflammation is prerequisite for dentin pulp complex repair and regeneration; otherwise, chronic disease or pulp necrosis occurs. Evaluation of pulp inflammation severity is necessary to predict the clinical success of maintaining pulp vitality. Clinical limitations to evaluating in situ inflammatory status are well-described. A molecular approach that aids clinical distinction between reversible and irreversible pulpitis could improve the success rate of vital pulp therapy. The aim of this article is to review inflammatory mediator expression in the context of clinical diagnosis.

Methods

We searched PubMed and Cochrane databases for articles published between 1970 and December 2016. Only published studies of inflammatory mediator expression related to clinical diagnosis were eligible for inclusion and analysis.

Results

Thirty-two articles were analyzed. Two molecular approaches were described by study methods, protein expression analysis and gene expression analysis. Our review indicates that interleukin-8, matrix metalloproteinase 9, tumor necrosis factor-α, and receptor for advanced glycation end products expression increase at both the gene and protein levels during inflammation.

Conclusions

Clinical irreversible pulpitis is related to specific levels of inflammatory mediator expression. The difference in expression between reversible and irreversible disease is both quantitative and qualitative. On the basis of our analysis, in situ quantification of inflammatory mediators may aid in the clinical distinction between reversible and irreversible pulpitis.

Section snippets

Methods

We performed a literature review of expression of any inflammatory mediators related to clinical diagnosis to create a list of potential expression patterns. This systematic review was conducted by using Preferred Reporting Items for Systematic reviews and Meta Analyses (PRISMA) guideline principles (24). The flow diagram of included records is shown in Figure 1. The focused question was proposed by using principle of Population, the Intervention (or exposure), the appropriate Control or

Selected Studies

This review included 32 articles (Table 1, Table 2). The analysis showed that authors used methods of messenger RNA or protein quantification of inflammatory mediators during inflammation; 28 addressed protein expression profiles 30, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 2 addressed gene expression profiles 71, 72, and 2 addressed both molecular and gene expression 73, 74.

Sampling Methods

Sampling involved tooth extraction in 24 articles 30,

Discussion

The main limitation of this study is the lack of quality studies. Furthermore, the variability in study methods and sample sizes are secondary limitations that preclude meta-analysis.

The results of this systematic review suggest that the gene and protein expression of IL-8, TNF-α, MMP-9, and RAGE increase inside pulp samples of teeth clinically diagnosed with irreversible symptomatic pulpitis.

IL-8 is produced by several pulpal cells including macrophages, lymphocytes, fibroblasts, and

Conclusion and Perspectives

Because dental pain descriptions are subjective, clinical diagnosis alone is unreliable to accurately determine pulp inflammation severity and pulp tissue ability to respond to endodontic procedures. As a result, pulp vital therapy is usually performed following empirical decision-making criteria. The need for new pulp diagnostic tools is increasingly evident. Molecular-based strategies are promising and may be relevant to determine appropriate clinical indications for vital pulp therapy and to

Acknowledgments

The authors deny any conflicts of interest related to this study.

References (102)

  • T. Izumi et al.

    Immunohistochemical study on the immunocompetent cells of the pulp in human non-carious and carious teeth

    Arch Oral Biol

    (1995)
  • I.E. Yaylali et al.

    Critical assessment of search strategies in systematic reviews in endodontics

    J Endod

    (2016)
  • C.R. Rauschenberger et al.

    Human polymorphonuclear granule components: relative levels detected by a modified enzyme-linked immunosorbent assay in normal and inflamed dental pulps

    J Endod

    (1991)
  • W.H. Pulver et al.

    Immune components in normal and inflamed human dental pulp

    Arch Oral Biol

    (1977)
  • S. Wakisaka et al.

    Substance P-like immunoreactivity in the pulp-dentine zone of human molar teeth demonstrated by indirect immunofluorescence

    Arch Oral Biol

    (1984)
  • I.A. El Karim et al.

    Vasoactive intestinal polypeptide (VIP) and VPAC1 receptor in adult human dental pulp in relation to caries

    Arch Oral Biol

    (2006)
  • V. Karapanou et al.

    Interleukin-8 is increased in gingival crevicular fluid from patients with acute pulpitis

    J Endod

    (2008)
  • E.H. Grutzner et al.

    Effect of injury on pulpal levels of immunoreactive substance P and immunoreactive calcitonin gene-related peptide

    J Endod

    (1992)
  • K. Gu et al.

    Expression of genes for bone morphogenetic proteins and receptors in human dental pulp

    Arch Oral Biol

    (1996)
  • S. Shi et al.

    Comparison of human dental pulp and bone marrow stromal stem cells by cDNA microarray analysis

    Bone

    (2001)
  • J. Caviedes-Bucheli et al.

    Expression of insulin-like growth factor-1 receptor in human pulp tissue

    J Endod

    (2004)
  • K. Takeda et al.

    Expression of bone morphogenetic protein genes in the human dental pulp cells

    Bone

    (1994)
  • M.M. Mendoza et al.

    An ultrastructural investigation of the human apical pulp in irreversible pulpitis: I—nerves

    J Endod

    (1987)
  • J.S. Cohen et al.

    A radioimmunoassay determination of the concentrations of prostaglandins E2 and F2alpha in painful and asymptomatic human dental pulps

    J Endod

    (1985)
  • M.E. Proctor et al.

    Determination and relationship of C-reactive protein in human dental pulps and in serum

    J Endod

    (1991)
  • C.L. Hahn et al.

    Antibodies in normal and diseased pulps reactive with microorganisms isolated from deep caries

    J Endod

    (1992)
  • C.R. Rauschenberger et al.

    Detection of human IL-2 in normal and inflamed dental pulps

    J Endod

    (1997)
  • G.T. Huang et al.

    Increased interleukin-8 expression in inflamed human dental pulps

    Oral Surg Oral Med Oral Pathol Oral Radiol Endod

    (1999)
  • L.M. Anderson et al.

    Evaluating IL-2 levels in human pulp tissue

    J Endod

    (2002)
  • S.J. Shin et al.

    Tissue levels of matrix metalloproteinases in pulps and periapical lesions

    J Endod

    (2002)
  • S. Pezelj-Ribaric et al.

    Detection of tumor necrosis factor alpha in normal and inflamed human dental pulps

    Arch Med Res

    (2002)
  • L. Artese et al.

    Vascular endothelial growth factor (VEGF) expression in healthy and inflamed human dental pulps

    J Endod

    (2002)
  • W.R. Bowles et al.

    Tissue levels of immunoreactive substance P are increased in patients with irreversible pulpitis

    J Endod

    (2003)
  • J. Caviedes-Bucheli et al.

    Expression of calcitonin gene-related peptide (CGRP) in irreversible acute pulpitis

    J Endod

    (2004)
  • T. Nakanishi et al.

    Expression of macrophage inflammatory protein 3alpha in human inflamed dental pulp tissue

    J Endod

    (2005)
  • M. Zehnder et al.

    A first study on the usefulness of matrix metalloproteinase 9 from dentinal fluid to indicate pulp inflammation

    J Endod

    (2011)
  • A. Abd-Elmeguid et al.

    Dentin matrix protein-1 activates dental pulp fibroblasts

    J Endod

    (2012)
  • T. Accorsi-Mendonça et al.

    Evaluation of gelatinases, tissue inhibitor of matrix metalloproteinase-2, and myeloperoxidase protein in healthy and inflamed human dental pulp tissue

    J Endod

    (2013)
  • A. Abd-Elmeguid et al.

    Osteocalcin expression in pulp inflammation

    J Endod

    (2013)
  • J. Mente et al.

    A prospective clinical pilot study on the level of matrix metalloproteinase-9 in dental pulpal blood as a marker for the state of inflammation in the pulp tissue

    J Endod

    (2016)
  • M. Zehnder et al.

    Cytokine gene expression: part of host defence in pulpitis

    Cytokine

    (2003)
  • C.H. Tsai et al.

    The upregulation of matrix metalloproteinase-9 in inflamed human dental pulps

    J Endod

    (2005)
  • C.L. Hahn et al.

    Innate immune responses of the dental pulp to caries

    J Endod

    (2007)
  • S. Zhai et al.

    Nemotic human dental pulp fibroblasts promote human dental pulp stem cells migration

    Exp Cell Res

    (2013)
  • H. Yang et al.

    The effects of tumor necrosis factor-α on mineralization of human dental apical papilla cells

    J Endod

    (2012)
  • H. Nagase et al.

    Matrix metalloproteinases

    J Biol Chem

    (1999)
  • L. Zheng et al.

    Matrix metalloproteinase-3 accelerates wound healing following dental pulp injury

    Am J Pathol

    (2009)
  • T. Okamoto et al.

    Increased expression of matrix metalloproteinase-9 and hepatocyte growth factor in the cerebrospinal fluid of infants with posthemorrhagic hydrocephalus

    Early Hum Dev

    (2010)
  • E. Maita et al.

    Fluid and protein flux across the pulpodentine complex of the dog in vivo

    Arch Oral Biol

    (1991)
  • K. Schmidlin et al.

    Complication and failure rates in patients treated for chronic periodontitis and restored with single crowns on teeth and/or implants

    Clin Oral Implants Res

    (2010)
  • Cited by (0)

    View full text