Odontoblasts
Protectors of the Smile
Credit: Art by Nelly Aghekyan. Set in motion by Dr. Emanuele Petretto. Words by Dr. Nowrin Ahmed. Coordinator: Dr. Masia Maksymowicz, Series Director: Dr. Radhika Patnala
#Extraordinarycelltypes #sciart #lifescience
Meet odontoblasts: cells commonly known for secreting dentin, which forms the bulk of our teeth, but also for orchestrating a fascinating array of functions from sensory to defensive immune responses (1). Here we explore the intricacies of what makes these cells so remarkable.
Odontoblast structure
Odontoblasts are highly polarized cells shaped like tall columns, of around 40–50 µm in length (2). They are arranged in a single layer around the outermost part of dental pulp, which is a living tissue rich in blood vessels that supplies odontoblasts with nutrients and oxygen, thus facilitating the production of dentin (3, 4). These cells possess cytoplasmic projections made of microtubules and filaments that extend into the predentin/dentin matrix. Additionally, they form a selective barrier between dentin and dental pulp through large junctional complexes and communicate with each other through gap junction proteins (5), mostly connexin 43, which is also suggested to be involved in tooth homeostasis (6). Their specialized morphology allows them to secrete dentin while creating a protective barrier between dentin and dental pulp. Since odontoblasts and dental pulp are intricately dependent on each other for their survival and growth, they are referred to as the dentin-pulp complex (7).
Odontoblast life cycle
Odontoblasts go through different stages in their life cycle which is characterized by differential secretion of dentin (8). During the initial phase of tooth development, odontoblasts are at their most active stage where they produce ‘primary dentin’. After the tooth has fully developed, these cells remove some of their secretory organelles to become mature odontoblasts that secrete ‘secondary dentin’ at a slower rate. Mature odontoblasts eventually reach the ‘old odontoblasts’ stage where the cell’s size and shape change (8). These different stages of odontoblasts are regulated by several transcription factors (9). Adult odontoblasts survive throughout the life of a tooth which is a unique characteristic also seen in neurons and myocardiocytes (1).
Dentinogenesis
Dentinogenesis is a continuous process by which odontoblasts produce dentin throughout the life of a tooth. It is composed mostly of collagen type I (90%), as well as collagen type III and type V. Non-collagenous proteins such as glycoproteins, proteoglycans, and dentin phosphoproteins are also present in dentin. Odontoblasts synthesize and secrete all proteins required to create the extracellular matrix predentin, an immature form of dentin, which becomes mineralized by non-collagenous proteins such as dentin phosphoproteins to fully develop into dentin. This unmineralized matrix, predentin, separates the odontoblast layer from the dentin layer (10). Odontoblasts not only secrete dentin at a rate of 4 µm per day until the tooth has fully grown, which takes about 2 years, but they also continue to maintain dentin secretion at a rate of 0.4 µm per day throughout the tooth’s lifespan (11).
Sensitivity to pain and heat
Odontoblasts can respond to external stimuli through nerve endings, mainly A-delta fibers and C fibers, from sensory neurons in the trigeminal ganglion (12). These nerve endings innervate 30–70% of the odontoblasts (13). During development, odontoblasts play an essential role in guiding nerve fibers into the dentin-pulp complex through signaling molecules such as semaphorin 7A (14). Interestingly, odontoblasts undergo age-dependent changes with a progressive decrease in nerve fibers in the dentin-pulp complex with aging, thus, leading to decreased sensitivity to pain and heat in teeth (15). Pain signals from the dental pulp play a protective role by initiating an immune response at the site of injury (16).
Protective role of odontoblasts
Odontoblasts serve as the first line of defence against pathogens, thus playing a crucial role in maintaining dental health. They are the primary guardians against bacteria invasion resulting from dental decay or injury (1). The layer of odontoblasts at the dentin-pulp interface protects the dental pulp through various mechanisms. Odontoblasts are equipped with specialized pattern recognition receptors (PPRs), such as toll-like receptor (TLR) and nucleotide-binding oligomerization domain (NOD), with which they recognize pathogen-associated molecular patterns (PAMPs) commonly found in pathogens (17, 18). Interestingly, it has been recently found that PPRs can also detect signals from damaged cells. Detection of pathogens initiates a cascade of signaling pathways that releases pro-inflammatory cytokines, chemokines, and type I interferon which initiates innate immune responses by recruiting immune cells such as immature dendritic cells and leukocytes (19,20). Additionally, odontoblasts can also respond to pathogenic invasions by synthesizing and releasing defensins, peptides capable of killing pathogens, as well as nitric oxide (19). While these cells are busy fighting off an infection, they lower their production of dentin matrix components such as collagen type I, highlighting their sophistication (20). Therefore, these cells play an essential role in maintaining dental health by fighting pathogens as well as activating the cell’s innate immune response.
Odontoblasts in diseases
Odontoblasts play a role in maintaining the health of the dental pulp by their regeneration. Not only do they fight pathogens involved in tooth decay or injury, but can also replace the damaged dentin layer by producing a layer of regenerated dentin (21). Additionally, damaged odontoblasts are replaced by newly differentiated odontoblasts originating from stem cells in dental pulp. This contributes to the formation of dentin that shields the dental pulp from further injury or exposure to pathogens (22). Therefore, the dentin-pulp complex has the potential to heal from injury due to this reactive dentinogenesis by odontoblasts (23). This regenerative property of odontoblasts is not fully understood and advances in our understanding of this process might open new therapeutic avenues for the treatment of dental disorders.
Lastly, some autosomally-inherited genetic disorders can cause defects in dentin formation. They can be grouped into two categories: dentinogenesis imperfecta where there are deficiencies in the formation of collagen and mineralization of dentin, and dentinogenesis dysplasia where the pulp chamber is destroyed (24). Examples of these disorders include dentinogenesis imperfecta type II which affects around 1:6,000 to 1:8,000 people in the US (25), and dentin dysplasia type I which is rare, affecting only 1:100,00 people (26).
The role of odontoblasts in dentin formation has been extensively studied, but their involvement in fighting pathogens and detecting external stimuli needs further examination, as mounting evidence suggests that these cells are capable of much more than dentinogenesis (1). Future studies should aim to provide a better understanding of odontoblast differentiation from dental stem cells, as there is potential for exciting therapeutic and clinical applications of the regenerative properties of odontoblasts.
Recognizing and appreciating the labs working in this space
- Eduardo Couve, Universidad de Valparaíso, Valparaíso, Chile.
- Penn Dental Medicine, University of Pennsylvania, USA. https://www.dental.upenn.edu/research/research-overview/ Twitter: @PennDentalMed
- Michael McCullough, The University of Melbourne, Melbourne, Australia. https://findanexpert.unimelb.edu.au/profile/14281-michael-mccullough
- Paul Cooper, University of Otago, Dunedin, New Zealand. https://www.otago.ac.nz/dentistry/departments/oral-sciences/oral-biology/profile?id=3228
- Ariane Berdal, Centre de Recherche des Cordeliers, INSERM, Paris, France. https://www.crcordeliers.fr/equipes/molecular-oral-pathophysiology/
- Carmen Carda and Amando Peydró, Tissue Engineering Laboratory, University of Valencia, Valencia, Spain. https://www.uv.es/scientific-technological-offer/en/research-groups/health/infectious-diseases-including-poverty-related-neglected-disease/research-group-histopathology-tissue-engineering-1286222584921/GrupsInves.html?id=1286254694184
- Françoise Bleicher, Laboratoire du Développement des Tissus Dentaires, ESPRI INSERM, Lyon, France.
- Takashi Matsuo, Tokushima University Graduate School, Tokushima, Japan.
- Michel Goldberg, Université René Descartes, Paris, France. https://t3s-1124.biomedicale.parisdescartes.fr/nos-publications-2/michel-golberg/
- Luciana F Massa, Laboratory of Mineralized Tissue Biology, University of São Paulo, São Paulo, Brazil. Twitter: @Invisalign_SP
- Kiyoko Watanabe, Kanagawa Dental College, Kanagawa, Japan.
References
1. Couve, E., R. Osorio, and O. Schmachtenberg. “The Amazing Odontoblast: Activity, Autophagy, and Aging.” J Dent Res 92 9 (2013): 765–72.
2. T Ten Cate, A. R. “The Role of Epithelium in the Development, Structure and Function of the Tissues of Tooth Support.” Oral Dis 2 1 (1996): 55–62.
3. Sasaki, T., and P. R. Garant. “Structure and Organization of Odontoblasts.” Anat Rec 245 2 (1996): 235–49.
4. Yoshida, S., and H. Ohshima. “Distribution and Organization of Peripheral Capillaries in Dental Pulp and Their Relationship to Odontoblasts.” Anat Rec 245 2 (1996): 313–26
5. Garant, P. R. “The Organization of Microtubules within Rat Odontoblast Processes Revealed by Perfusion Fixation with Glutaraldehyde.” Arch Oral Biol 17 7 (1972): 1047–58.
6. Fried, K., et al. “Combinatorial Expression Patterns of the Connexins 26, 32, and 43 During Development, Homeostasis, and Regeneration of Rat Teeth.” Int J Dev Biol 40 5 (1996): 985–95.
7. Rajan, S., et al. “Post-Mitotic Odontoblasts in Health, Disease, and Regeneration.” Arch Oral Biol 109 (2020): 104591.
8. Couve, E. “Ultrastructural Changes During the Life Cycle of Human Odontoblasts.” Arch Oral Biol 31 10 (1986): 643–51.
9. Simon, S., et al. “Molecular Characterization of Young and Mature Odontoblasts.” Bone 45 4 (2009): 693–703.
10. Goldberg, M., et al. “Dentin: Structure, Composition and Mineralization.” Front Biosci (Elite Ed) 3 2 (2011): 711–35
11. Yogesh, P. B., et al. “Invivo Comparative Evaluation of Tertiary Dentin Deposit to Three Different Luting Cements a Histopathological Study.” J Indian Prosthodont Soc 13 3 (2013): 205–11
12. Byers, M. R., and M. V. Närhi. “Dental Injury Models: Experimental Tools for Understanding Neuroinflammatory Interactions and Polymodal Nociceptor Functions.” Crit Rev Oral Biol Med 10 1 (1999): 4–39.
13. Carda, C., and A. Peydró. “Ultrastructural Patterns of Human Dentinal Tubules, Odontoblasts Processes and Nerve Fibres.” Tissue Cell 38 2 (2006): 141–50.
14. Maurin, J. C., et al. “Odontoblast Expression of Semaphorin 7a During Innervation of Human Dentin.” Matrix Biol 24 3 (2005): 232–8.
15. Bernick, S. “Effect of Aging on the Nerve Supply to Human Teeth.” J Dent Res 46 4 (1967): 694–9.
16. Hahn, C. L., and F. R. Liewehr. “Innate Immune Responses of the Dental Pulp to Caries.” J Endod 33 6 (2007): 643–51.
17. Mutoh, N., et al. “Expression of Toll-Like Receptor 2 and 4 in Dental Pulp.” J Endod 33 10 (2007): 1183–6.
18. Hosokawa, Y., et al. “Functional Roles of Nod1 in Odontoblasts on Dental Pulp Innate Immunity.” Biomed Res Int 2016 (2016): 9325436.
19. Yumoto, H., et al. “The Roles of Odontoblasts in Dental Pulp Innate Immunity.” Jpn Dent Sci Rev 54 3 (2018): 105–17.
20. Durand, S. H., et al. “Lipoteichoic Acid Increases Tlr and Functional Chemokine Expression While Reducing Dentin Formation in in Vitro Differentiated Human Odontoblasts.” J Immunol 176 5 (2006): 2880–7.
21. Smith, A. J., et al. “Reactionary Dentinogenesis.” Int J Dev Biol 39 1 (1995): 273–80.
22. Gronthos, S., et al. “Postnatal Human Dental Pulp Stem Cells (Dpscs) in Vitro and in Vivo.” Proc Natl Acad Sci U S A 97 25 (2000): 13625–30.
23. Farges, J. C., et al. “Dental Pulp Defence and Repair Mechanisms in Dental Caries.” Mediators Inflamm 2015 (2015): 230251.
24. Arana-Chavez, V. E., and L. F. Massa. “Odontoblasts: The Cells Forming and Maintaining Dentine.” Int J Biochem Cell Biol 36 8 (2004): 1367–73.
25. Witkop, C. J., Jr. “Hereditary Defects of Dentin.” Dent Clin North Am 19 1 (1975): 25–45.
26. Kim, J. W., and J. P. Simmer. “Hereditary Dentin Defects.” J Dent Res 86 5 (2007): 392–9.
About the author:
Dr. Nowrin Ahmed
Content Editor The League of Extraordinary Cell Types, Sci-Illustrate Stories
Dr. Nowrin Ahmed has a PhD in Behavioral and Neural Sciences from Rutgers University-Newark (NJ, USA) where she studied the interactions between the midline thalamus and the amygdala. Currently, she is a post-doctoral fellow at Rutgers University — Newark where she is studying amygdala circuits. Dr. Nowrin enjoys sharing the beauty of science with diverse audiences.
About the artist:
NELLY AGHEKYAN
Contributing Artist The League of Extraordinary Cell Types, Sci-Illustrate Stories
Nelli Aghekyan, did a bachelor’s and master’s in Architecture in Armenia, after studying architecture and interior design for 6 years, she concentrated on her drawing skills and continued her path in the illustration world. She works mainly on children’s book illustrations, some of her books are now being published. Currently living in Italy, she works as a full-time freelance artist, collaborating with different companies and clients.
About the animator:
DR. EMANUELE PETRETTO
Animator The League of Extraordinary Cell Types, Sci-Illustrate Stories
Dr. Petretto received his Ph.D. in Biochemistry at the University of Fribourg, Switzerland, focusing on the behavior of matter at nanoscopic scales and the stability of colloidal systems. Using molecular dynamics simulations, he explored the delicate interaction among particles, interfaces, and solvents.
Currently, he is fully pursuing another delicate interaction: the intricate interplay between art and science. Through data visualization, motion design, and games, he wants to show the wonders of the complexity surrounding us.
About the series:
The League of Extraordinary Cell types
The team at Sci-Illustrate and Endosymbiont bring to you an exciting series where we dive deep into the wondrous cell types in our body, that make our hearts tick ❤.
