Review
Post-mitotic odontoblasts in health, disease, and regeneration

https://doi.org/10.1016/j.archoralbio.2019.104591Get rights and content

Highlights

  • The four stages in odontoblast cell life cycle from pre-odontoblast to old odontoblast stage.

  • An update of odontoblasts’ role in innate immunity.

  • An update on the potential roles of biological markers used in diagnosis and treatment of the diseased pulp.

  • An overview of current trends in regenerative dental medicine used in pulp therapy in vital and non-vital teeth.

Abstract

Objective

Description of the odontoblast lifecycle, an overview of the known complex molecular interactions that occur when the health of the dental pulp is challenged and the current and future management strategies on vital and non-vital teeth.

Methods

A literature search of the electronic databases included MEDLINE (1966-April 2019), CINAHL (1982-April 2019), EMBASE and EMBASE Classic (1947-April 2019), and hand searches of references retrieved were undertaken using the following MESH terms ‘odontoblast*’, ‘inflammation’, ‘dental pulp*’, ‘wound healing’ and ‘regenerative medicine’.

Results

Odontoblasts have a sensory and mechano-transduction role so as to detect external stimuli that challenge the dental pulp. On detection, odontoblasts stimulate the innate immunity by activating defence mechanisms key in the healing and repair mechanisms of the tooth. A better understanding of the role of odontoblasts within the dental pulp complex will allow an opportunity for biological management to remove the cause of the insult to the dental pulp, modulate the inflammatory process, and promote the healing and repair capabilities of the tooth. Current strategies include use of conventional dental pulp medicaments while newer methods include bioactive molecules, epigenetic modifications and tissue engineering.

Conclusion

Regenerative medicine methods are in their infancy and experimental stages at best. This review highlights the future direction of dental caries management and consequently research.

Introduction

The National Institute of Dental and Craniofacial Research defines that regenerative medicine harnesses the body’s growth and healing properties to repair or replace damaged cells, tissues, or organs. Researchers are drawing on the fields of stem cell and developmental biology, bioengineering, material science, and gene editing, among others, to develop safe and effective regenerative therapies (NIDCR, 2018).

Currently in dentistry, the main cells that are targeted in regenerative dental medicine are the odontoblasts and dental pulp stem cells. The growth and healing properties of the vital dental pulp complex is assisted by the application of bioactive materials. The replacement of damaged dental pulp complex is the research related to tissue engineering. Regenerative endodontics is ‘biologically based procedures designed to replace damaged tooth structure, including dentine and root structure, as well as cells of the pulp-dentine complex’ (Murray, Garcia-Godoy, & Hargreaves, 2007).

Odontoblasts are post-mitotic cells that are maintained throughout the life of a tooth until cell death occurs by either trauma, disease or apoptosis. Their primary role is the deposition of primary, secondary and tertiary dentine in teeth. However, they also play a critical role in physiological maintenance of the pulp, and in the event of injury, have the ability to trigger a defensive immune response assisting the tooth to heal and repair (tertiary dentine). This timely review provides an overview of current knowledge in the odontoblast life-cycle and their role in innate immunity that will help clinicians and researchers develop reproducible chairside methods so as to diagnose dental pulp disease accurately. Subsequently, to utilise this knowledge for the application of current regenerative medicine approaches to assist odontoblasts in healing and repair after removal of the causative factor of the disease. The trends and potential methods using bioactive molecules, epigenetic modifications and tissue engineering will be reviewed.

Section snippets

Methods

A literature search was conducted using the following electronic databases MEDLINE via OVID (1966-April 2019), CINAHL (1982-April 2019), EMBASE and EMBASE CLASSIC (1947-APRIL 2019) and hand searches of references retrieved. The search strategy used was replicated for all electronic databases, was first conducted and up to and including April 2019. The search strategy used the following MESH keywords; ‘odontoblast*’, ‘inflammation’, ‘dental pulp*’, ‘wound healing’, ‘regenerative medicine’,

Conclusion

Regenerative dental medicine has provided many new possibilities for the future management of dental caries and its sequelae. Understanding the molecular and genetic interactions within the dental pulp complex in health and disease will assist researchers to fine-tune the available methods in bioactive materials, molecules, epigenetic modifications and bioengineering. It is our hope that in the near future we may be able to heal or regenerate the dental pulp to help preserve structurally sound

Author contribution

SR, AL, DJM, AEB and MM conceived and developed the idea as part of the literature review for SR’s PhD thesis. All authors reviewed and approved the final version of the manuscript.

Declaration of Competing Interest

None.

References (98)

  • M. Goldberg et al.

    Inflammatory and immunological aspects of dental pulp repair

    Pharmacological Research

    (2008)
  • K. Hartmann et al.

    C3a and C5a stimulate chemotaxis of human mast cells

    Blood

    (1997)
  • C.C. Hu et al.

    Reparative dentin formation in rat molars after direct pulp capping with growth factors

    Journal of Endodontics

    (1998)
  • T. Hui et al.

    EZH2, apotential regulator of dentalpulp inflammation and regeneration

    Journal of Endodontics

    (2014)
  • S. Kakehashi et al.

    The effects of surgical exposures of dental pulps in germ-free and conventional laboratory rats

    Oral Surgery, Oral Medicine, and Oral Pathology

    (1965)
  • A.A. Khan et al.

    Effect of calcium hydroxide on proinflammatory cytokines and neuropeptides

    Journal of Endodontics

    (2008)
  • P.E. Murray et al.

    Regenerative endodontics: A review of current status and a call for action

    Journal of Endodontics

    (2007)
  • K. Narayanan et al.

    Dentin matrix protein 1 regulates dentin sialophosphoprotein gene transcription during early odontoblast differentiation

    The Journal of Biological Chemistry

    (2006)
  • M. Pigg et al.

    Validity of preoperative clinical findings to identify dental pulp status: A national dental practice-based research network study

    Journal of Endodontics

    (2016)
  • C. Prati et al.

    Calcium silicate bioactive cements: Biological perspectives and clinical applications

    Dental Materials

    (2015)
  • D. Ricucci et al.

    Correlation between clinical and histologic pulp diagnoses

    Journal of Endodontics

    (2014)
  • D.C. Rubinsztein et al.

    Autophagy and aging

    Cell

    (2011)
  • P. Rufas et al.

    Complement C3a mobilizes dental pulp stem cells and specifically guides pulp fibroblast recruitment

    Journal of Endodontics

    (2016)
  • R.B. Rutherford et al.

    Induction of reparative dentine formation in monkeys by recombinant human osteogenic protein-1

    Archives of Oral Biology

    (1993)
  • J.J. Segura et al.

    Calcium hydroxide inhibits substrate adherence capacity of macrophages

    Journal of Endodontics

    (1997)
  • S. Seltzer et al.

    The dynamics of pulp inflammation: Correlations between diagnostic data and actual histologic findings in the pulp

    Oral Surgery, Oral Medicine, and Oral Pathology

    (1963)
  • S. Simon et al.

    The MAP kinase pathway is involved in odontoblast stimulation via p38 phosphorylation

    Journal of Endodontics

    (2010)
  • S. Simon et al.

    Molecular characterization of young and mature odontoblasts

    Bone

    (2009)
  • A.J. Smith et al.

    Exploiting the bioactive properties of the dentin-pulp complex in regenerative endodontics

    Journal of Endodontics

    (2016)
  • A.J. Smith et al.

    Harnessing the natural regenerative potential of the dental pulp

    Dental Clinics of North America

    (2012)
  • N.A. Taha et al.

    Full pulpotomy with biodentine in symptomatic young permanent teeth with carious exposure

    Journal of Endodontics

    (2018)
  • N.A. Taha et al.

    Partial pulpotomy in mature permanent teeth with clinical signs indicative of irreversible pulpitis: A randomized clinical trial

    Journal of Endodontics

    (2017)
  • H.J. Tong et al.

    Regenerative endodontic therapy in the management of nonvital immature permanent teeth: A systematic review-outcome evaluation and meta-analysis

    Journal of Endodontics

    (2017)
  • D. Tziafas et al.

    Effects of recombinant basic fibroblast growth factor, insulin-like growth factor-II and transforming growth factor-beta 1 on dog dental pulp cells in vivo

    Archives of Oral Biology

    (1998)
  • C.D. Allis et al.

    The molecular hallmarks of epigenetic control

    Nature Reviews Genetics

    (2016)
  • H. Bakhtiar et al.

    The role of stem cell therapy in regeneration of dentine-pulp complex: a systematic review

    Progress in Biomaterials

    (2018)
  • C. Begue-Kirn et al.

    Dentin sialoprotein, dentin phosphoprotein, enamelysin and ameloblastin: Tooth-specific molecules that are distinctively expressed during murine dental differentiation

    European Journal of Oral Sciences

    (1998)
  • W.T. Butler

    Dentin matrix proteins and dentinogenesis

    Connective Tissue Research

    (1995)
  • M.R. Byers et al.

    Dental injury models: Experimental tools for understanding neuroinflammatory interactions and polymodal nociceptor functions

    Critical Reviews in Oral Biology & Medicine

    (1999)
  • M.R. Byers et al.

    Dental neuroplasticity, neuro-pulpal interactions, and nerve regeneration

    Microscopy Research and Technique

    (2003)
  • L.E. Chávez de Paz et al.

    Microbiology and immunology of endodontic infections

  • F. Chmilewsky et al.

    Pulp progenitor cell recruitment is selectively guided by a C5a gradient

    Journal of Dental Research

    (2013)
  • E. Couve et al.

    The amazing odontoblast: Activity, autophagy, and aging

    Journal of Dental Research

    (2013)
  • W.L.O. da Rosa et al.

    Disclosing the physiology of pulp tissue for vital pulp therapy

    International Endodontic Journal

    (2018)
  • K. Dobie et al.

    Effects of alginate hydrogels and TGF-beta 1 on human dental pulp repair in vitro

    Connective Tissue Research

    (2002)
  • P.M. Dummer et al.

    Clinical signs and symptoms in pulp disease

    International Endodontic Journal

    (1980)
  • J.C. Farges et al.

    Dental pulp defence and repair mechanisms in dental caries

    Mediators of Inflammation

    (2015)
  • A. George et al.

    Phosphorylated proteins and control over apatite nucleation, crystal growth, and inhibition

    Chemical Reviews

    (2008)
  • T. Giraud et al.

    Pulp capping materials modulate the balance between inflammation and regeneration

    Dental Materials

    (2018)
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