ReviewPost-mitotic odontoblasts in health, disease, and regeneration
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)
- et al.
Identification of secretory odontoblasts using DMP1-GFP transgenic mice
Bone
(2011) Odontoblast physiology
Experimental Cell Research
(2014)- et al.
Methylation pattern of the IFN-gamma gene in human dental pulp
Journal of Endodontics
(2010) - et al.
Comparative analysis of transforming growth factor-beta isoforms 1-3 in human and rabbit dentine matrices
Archives of Oral Biology
(1997) - et al.
Inflammation and regeneration in the dentin-pulp complex: A double-edged sword
Journal of Endodontics
(2014) Ultrastructural changes during the life cycle of human odontoblasts
Archives of Oral Biology
(1986)- et al.
Regenerative endodontic procedures: Clinical outcomes
Dental Clinic of North America
(2017) - et al.
Activation of human neutrophils by C3a and C5A. Comparison of the effects on shape changes, chemotaxis, secretion, and respiratory burst
FEBS Letters
(1994) - et al.
Methylation and demethylation in the regulation of genes, cells, and responses in the immune system
Clinical Immunology
(2003) - et al.
Dental-pulp Pathosis - clinicopathologic correlations based on 109 cases
Oral Surgery Oral Medicine Oral Pathology Oral Radiology and Endodontology
(1973)
Inflammatory and immunological aspects of dental pulp repair
Pharmacological Research
C3a and C5a stimulate chemotaxis of human mast cells
Blood
Reparative dentin formation in rat molars after direct pulp capping with growth factors
Journal of Endodontics
EZH2, apotential regulator of dentalpulp inflammation and regeneration
Journal of Endodontics
The effects of surgical exposures of dental pulps in germ-free and conventional laboratory rats
Oral Surgery, Oral Medicine, and Oral Pathology
Effect of calcium hydroxide on proinflammatory cytokines and neuropeptides
Journal of Endodontics
Regenerative endodontics: A review of current status and a call for action
Journal of Endodontics
Dentin matrix protein 1 regulates dentin sialophosphoprotein gene transcription during early odontoblast differentiation
The Journal of Biological Chemistry
Validity of preoperative clinical findings to identify dental pulp status: A national dental practice-based research network study
Journal of Endodontics
Calcium silicate bioactive cements: Biological perspectives and clinical applications
Dental Materials
Correlation between clinical and histologic pulp diagnoses
Journal of Endodontics
Autophagy and aging
Cell
Complement C3a mobilizes dental pulp stem cells and specifically guides pulp fibroblast recruitment
Journal of Endodontics
Induction of reparative dentine formation in monkeys by recombinant human osteogenic protein-1
Archives of Oral Biology
Calcium hydroxide inhibits substrate adherence capacity of macrophages
Journal of Endodontics
The dynamics of pulp inflammation: Correlations between diagnostic data and actual histologic findings in the pulp
Oral Surgery, Oral Medicine, and Oral Pathology
The MAP kinase pathway is involved in odontoblast stimulation via p38 phosphorylation
Journal of Endodontics
Molecular characterization of young and mature odontoblasts
Bone
Exploiting the bioactive properties of the dentin-pulp complex in regenerative endodontics
Journal of Endodontics
Harnessing the natural regenerative potential of the dental pulp
Dental Clinics of North America
Full pulpotomy with biodentine in symptomatic young permanent teeth with carious exposure
Journal of Endodontics
Partial pulpotomy in mature permanent teeth with clinical signs indicative of irreversible pulpitis: A randomized clinical trial
Journal of Endodontics
Regenerative endodontic therapy in the management of nonvital immature permanent teeth: A systematic review-outcome evaluation and meta-analysis
Journal of Endodontics
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
The molecular hallmarks of epigenetic control
Nature Reviews Genetics
The role of stem cell therapy in regeneration of dentine-pulp complex: a systematic review
Progress in Biomaterials
Dentin sialoprotein, dentin phosphoprotein, enamelysin and ameloblastin: Tooth-specific molecules that are distinctively expressed during murine dental differentiation
European Journal of Oral Sciences
Dentin matrix proteins and dentinogenesis
Connective Tissue Research
Dental injury models: Experimental tools for understanding neuroinflammatory interactions and polymodal nociceptor functions
Critical Reviews in Oral Biology & Medicine
Dental neuroplasticity, neuro-pulpal interactions, and nerve regeneration
Microscopy Research and Technique
Microbiology and immunology of endodontic infections
Pulp progenitor cell recruitment is selectively guided by a C5a gradient
Journal of Dental Research
The amazing odontoblast: Activity, autophagy, and aging
Journal of Dental Research
Disclosing the physiology of pulp tissue for vital pulp therapy
International Endodontic Journal
Effects of alginate hydrogels and TGF-beta 1 on human dental pulp repair in vitro
Connective Tissue Research
Clinical signs and symptoms in pulp disease
International Endodontic Journal
Dental pulp defence and repair mechanisms in dental caries
Mediators of Inflammation
Phosphorylated proteins and control over apatite nucleation, crystal growth, and inhibition
Chemical Reviews
Pulp capping materials modulate the balance between inflammation and regeneration
Dental Materials
Cited by (6)
Dental Pulp Fibroblast: A Star Cell
2022, Journal of EndodonticsCitation Excerpt :Further, DPFs can play important roles in pulp-dentin complex regeneration90, as emphasized in the following subsections. Odontoblasts are considered postmitotic cells143 with no potential for self-renewal. Severe carious lesions, traumatic injuries, or aggressive restorative procedures can cause irreversible damage, such as apoptosis144.
Exosomes derived from human dental stem cell enhance the viability of odontoblasts
2023, Nanomedicine Research JournalAutophagy in aging-related oral diseases
2022, Frontiers in EndocrinologyPro-inflammatory mediators expression by pulp cells following tooth whitening on restored enamel surface
2022, Brazilian Dental JournalThe role of dendritic cells during physiological and pathological dentinogenesis
2021, Journal of Clinical Medicine