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International Journal of Molecular... May 2024It is remarkable how teeth maintain their healthy condition under exceptionally high levels of mechanical loading. This suggests the presence of inherent mechanical... (Review)
Review
It is remarkable how teeth maintain their healthy condition under exceptionally high levels of mechanical loading. This suggests the presence of inherent mechanical adaptation mechanisms within their structure to counter constant stress. Dentin, situated between enamel and pulp, plays a crucial role in mechanically supporting tooth function. Its intermediate stiffness and viscoelastic properties, attributed to its mineralized, nanofibrous extracellular matrix, provide flexibility, strength, and rigidity, enabling it to withstand mechanical loading without fracturing. Moreover, dentin's unique architectural features, such as odontoblast processes within dentinal tubules and spatial compartmentalization between odontoblasts in dentin and sensory neurons in pulp, contribute to a distinctive sensory perception of external stimuli while acting as a defensive barrier for the dentin-pulp complex. Since dentin's architecture governs its functions in nociception and repair in response to mechanical stimuli, understanding dentin mechanobiology is crucial for developing treatments for pain management in dentin-associated diseases and dentin-pulp regeneration. This review discusses how dentin's physical features regulate mechano-sensing, focusing on mechano-sensitive ion channels. Additionally, we explore advanced in vitro platforms that mimic dentin's physical features, providing deeper insights into fundamental mechanobiological phenomena and laying the groundwork for effective mechano-therapeutic strategies for dentinal diseases.
Topics: Dentin; Humans; Animals; Odontoblasts; Mechanotransduction, Cellular; Biomechanical Phenomena; Dental Pulp; Extracellular Matrix
PubMed: 38891829
DOI: 10.3390/ijms25115642 -
The Journal of Histochemistry and... May 2011Dental pulp elaborates both bone and dentin under pathological conditions such as tooth replantation/transplantation. This study aims to clarify the expression of...
Dental pulp elaborates both bone and dentin under pathological conditions such as tooth replantation/transplantation. This study aims to clarify the expression of granulocyte macrophage colony-stimulating factor (GM-CSF) and osteopontin (OPN) in the process of reparative dentin formation by allogenic tooth transplantation using in situ hybridization for OPN and immunohistochemistry for GM-CSF and OPN at both levels of light and electron microscopes. Following the extraction of the mouse molar, the roots and pulp floor were resected and immediately allografted into the sublingual region. On days 1 to 3, immunocompetent cells such as macrophages and dendritic cells expressed both GM-CSF and OPN, and some of them were arranged along the pulp-dentin border and extended their cellular processes into the dentinal tubules. On days 5 to 7, tubular dentin formation commenced next to the preexisting dentin at the pulp horn where nestin-positive odontoblast-like cells were arranged. Until day 14, bone-like tissue formation occurred in the pulp chamber, where OPN-positive osteoblasts surrounded the bone matrix. These results suggest that the secretion of GM-CSF and OPN by immunocompetent cells such as macrophages and dendritic cells plays a role in the maturation of dendritic cells and the differentiation of odontoblasts, respectively, in the regenerated pulp tissue following tooth transplantation.
Topics: Animals; Cell Differentiation; Dendritic Cells; Dental Pulp; Dentin; Granulocyte-Macrophage Colony-Stimulating Factor; Histocompatibility Antigens Class II; Immunohistochemistry; In Situ Hybridization; Macrophages; Mice; Mice, Inbred ICR; Molar; Mouth Floor; Odontoblasts; Osteopontin; Transplantation, Homologous
PubMed: 21430263
DOI: 10.1369/0022155411403314 -
Developmental Dynamics : An Official... Feb 2011Wnt/β-catenin signaling is essential for tooth development beyond the bud stage, but little is known about the role of non-canonical Wnt signaling in odontogenesis....
Wnt/β-catenin signaling is essential for tooth development beyond the bud stage, but little is known about the role of non-canonical Wnt signaling in odontogenesis. Here we compared the expression of Wnt5a, a representative of noncanonical Wnts, with that of Ror2, the Wnt5a receptor for non-canonical signaling, in the developing tooth, and analyzed tooth phenotype in Wnt5a mutants. Wnt5a-deficient mice exhibit retarded tooth development beginning from E16.5, leading to the formation of smaller and abnormally patterned teeth with a delayed odontoblast differentiation at birth. These defects are associated with upregulated Axin2 and Shh expression in the dental epithelium and reduced levels of cell proliferation in the dental epithelium and mesenchyme. Retarded tooth development and defective odontoblast differentiation were also observed in Ror2 mutant mice. Our results suggest that Wnt5a regulates growth, patterning, and odontoblast differentiation during odontogenesis, at least partially by modulating Wnt/β-catenin canonical signaling.
Topics: Animals; Axin Protein; Cell Differentiation; Cell Proliferation; Cytoskeletal Proteins; Female; Mice; Mice, Knockout; Odontoblasts; Odontogenesis; Phenotype; Pregnancy; Receptor Tyrosine Kinase-like Orphan Receptors; Signal Transduction; Tooth; Wnt Proteins; Wnt-5a Protein; beta Catenin
PubMed: 21246660
DOI: 10.1002/dvdy.22550 -
Archives of Oral Biology Mar 2012Bcl-2 is widely expressed in a developing tooth organ and regulates tooth morphogenesis. However, whether Bcl-2 is related to tooth damage repair is unknown yet. Using...
OBJECTIVE
Bcl-2 is widely expressed in a developing tooth organ and regulates tooth morphogenesis. However, whether Bcl-2 is related to tooth damage repair is unknown yet. Using an odontoblast-targeted Bcl-2 overexpression transgenic mouse (Col2.3Bcl-2) and artificial cavity preparation as a model system, the relationship between Bcl-2 and reparative dentinogenesis is investigated in this study.
METHODS
The odontoblastic-like cell cultures derived from mouse molar pulps were established. The expression of transgenic human Bcl-2 (hBcl-2) and endogenous mouse Bcl-2 (mBcl-2) and mouse Bax (mBax, a Bcl-2 antagonist) was detected in vivo and in vitro by Western blot and immunocytochemistry, respectively. Basal level and artificial cavity-induced odontoblast apoptosis was detected by the Deoxynucleotidyl Transferase (TdT) dUTP Nick End labelling (TUNEL) technique. Reparative dentine formation induced by artificial cavity drilled to a half dentine thickness on mesial cervical region of mandibular first molars 2, 4, and 6 weeks post-op was evaluated histologically and via micro-CT.
RESULTS
The transgenic hBcl-2 was stably expressed in odontoblasts of the transgenic animals without interference with the expression of mBcl-2 and mBax. Basal level as well as artificial cavity- induced odontoblast apoptosis was prevented by the transgene. Compared to the wild type, the transgenic animals produced reparative dentine with significantly higher mineral density 6 weeks after the operation.
CONCLUSIONS
Bcl-2 overexpression prevents odontoblast apoptosis and promotes dentine damage repair, indicating that genetic manipulation of Bcl-2 may be a novel strategy to maintain the vitality and function of dentine-pulp complex under detrimental mechanical stimuli.
Topics: Animals; Apoptosis; Blotting, Western; Dental Caries; Dental Pulp; Dentin, Secondary; Dentinogenesis; Genes, bcl-2; Humans; In Situ Nick-End Labeling; Mice; Mice, Transgenic; Odontoblasts; Proto-Oncogene Proteins c-bcl-2; Wound Healing
PubMed: 21930259
DOI: 10.1016/j.archoralbio.2011.08.022 -
Modulators of Wnt Signaling Pathway Implied in Dentin Pulp Complex Engineering: A Literature Review.International Journal of Molecular... Sep 2022The main goal of vital pulp therapy (VPT) is to preserve the vitality of the pulp tissue, even when it is exposed due to bacterial invasion, iatrogenic mechanical... (Review)
Review
The main goal of vital pulp therapy (VPT) is to preserve the vitality of the pulp tissue, even when it is exposed due to bacterial invasion, iatrogenic mechanical preparation, or trauma. The type of new dentin formed as a result of VPT can differ in its cellular origin, its microstructure, and its barrier function. It is generally agreed that the new dentin produced by odontoblasts (reactionary dentin) has a tubular structure, while the dentin produced by pulp cells (reparative dentin) does not or has less. Thus, even VPT aims to maintain the vitality of the pulp. It does not regenerate the dentin pulp complex integrity. Therefore, many studies have sought to identify new therapeutic strategies to successfully regenerate the dentin pulp complex. Among them is a Wnt protein-based strategy based on the fact that Wnt proteins seem to be powerful stem cell factors that allow control of the self-renewal and proliferation of multiple adult stem cell populations, suitable for homeostasis maintenance, tissue healing, and regeneration promotion. Thus, this review outlines the different agents targeting the Wnt signaling that could be applied in a tooth environment, and could be a potential therapy for dentin pulp complex and bone regeneration.
Topics: Adult; Dental Pulp; Dentin; Humans; Odontoblasts; Stem Cells; Wnt Proteins; Wnt Signaling Pathway
PubMed: 36142496
DOI: 10.3390/ijms231810582 -
The Bulletin of Tokyo Dental College Feb 2007Pain serves as a warning of impending injury, triggering appropriate protective responses. Emotional and cognitive processing in the brain is involved in the sensation... (Review)
Review
Pain serves as a warning of impending injury, triggering appropriate protective responses. Emotional and cognitive processing in the brain is involved in the sensation of pain. As Ca(2+) waves in keratinocytes are mediated by the release of extracellular molecules such as signaling molecules, this may also affect the activity of surrounding cells such as sensory neurons. Although no junctions have been found between keratinocytes and sensory termini, ultrastructural studies have shown that keratinocytes come into contact with dorsal root ganglion neurons through membrane-membrane apposition. There is also indirect evidence that keratinocytes communicate with sensory neurons via extracellular molecules. Sensory neurons themselves sense various external stimuli, but there may also be skin-derived regulatory mechanisms by which sensory signaling is modulated.First, we will give a general outline of the subject: 1) Progress in identifying cortical loci that process pain messages is needed. 2) Far greater advances have been made in understanding the molecular mechanisms whereby primary sensory neurons detect pain-producing stimuli. 3) Genetic studies have facilitated the identification and functional characterization of molecules. 4) Now, the relationship between sensory and ion channels has become clear.
Topics: Adenosine Triphosphate; Animals; Brain Mapping; Facial Pain; Humans; Keratinocytes; Odontoblasts; Palate; Rats; Receptors, Calcium-Sensing; Somatosensory Cortex; TRPV Cation Channels; Tongue
PubMed: 17721061
DOI: 10.2209/tdcpublication.48.1 -
Advances in Dental Research Jul 2011Multipotency is a defining characteristic of post-natal stem cells. The human dental pulp contains a small subpopulation of stem cells that exhibit multipotency, as... (Review)
Review
Multipotency is a defining characteristic of post-natal stem cells. The human dental pulp contains a small subpopulation of stem cells that exhibit multipotency, as demonstrated by their ability to differentiate into odontoblasts, neural cells, and vascular endothelial cells. These discoveries highlight the fundamental role of stem cells in the biology of the dental pulp and suggest that these cells are uniquely suited for dental pulp tissue-engineering purposes. The availability of experimental approaches specifically designed for studies of the differentiation potential of dental pulp stem cells has played an important role in these discoveries. The objective of this review is to describe the development and characterization of the Tooth Slice/Scaffold Model of Dental Pulp Tissue Engineering. In addition, we discuss the multipotency of dental pulp stem cells, focusing on the differentiation of these cells into functional odontoblasts and into vascular endothelial cells.
Topics: Cell Differentiation; Dental Pulp; Endothelial Cells; Endothelium, Vascular; Humans; Multipotent Stem Cells; Neurons; Odontoblasts; Regeneration; Tissue Engineering; Tissue Scaffolds; Tooth
PubMed: 21677087
DOI: 10.1177/0022034511405325 -
The International Journal of... Feb 1995Based on recent literature, the specific potential of mature pulp cells to differentiate into polarized cells able to elaborate reparative dentin is described. These... (Review)
Review
Based on recent literature, the specific potential of mature pulp cells to differentiate into polarized cells able to elaborate reparative dentin is described. These odontoblast-like cells are distinguished, by morphological criteria, from the other matrix-formative cells involved in non-specific defensive mechanisms of dental pulp. The suitable tissue conditions and the normal cascade of reparative events, allowing initiation of dentinogenesis in sites of amputated pulp, are presented. This is followed by a review of current observations on specific dentinogenic events, induced in various culture systems or in intrapulpal sites of mature teeth by artificial bio-molecules or bio-matrices. Data from these experiments are focused on the role of extracellular matrix molecules and growth factors in acquisition of the odontoblast-like cell phenotype and initiation of reparative dentinogenesis.
Topics: Animals; Cell Differentiation; Dental Pulp; Dentin; Dentinogenesis; Humans; Odontoblasts; Wound Healing
PubMed: 7626418
DOI: No ID Found -
Scientific Reports Jan 2023Ascorbic acid (AA; vitamin C) plays a crucial role in the biosynthesis and secretion of collagen to produce the organic matrix of hard tissues. Nevertheless, the...
Ascorbic acid (AA; vitamin C) plays a crucial role in the biosynthesis and secretion of collagen to produce the organic matrix of hard tissues. Nevertheless, the detailed mechanism by which AA induces reparative dentinogenesis is still unknown. This study aimed to investigate the pathway and function of AA during wound healing in a rat pulpotomy model. Sodium-dependent vitamin C transporter (SVCT) 2 and glucose transporter (GLUT) 1 were detected in odontoblasts, endothelial cells, and nerve fibers in normal pulp tissues. SVCT2 and GLUT1 were also expressed in odontoblast-like cells in pulpotomized tissues of Wistar rats, and immunopositive cells of SVCT2 were significantly increased at 5 days after pulpotomy (p < 0.05). By contrast, osteogenic disorder Shionogi (ODS) rats, which cannot generate AA, also expressed SVCT2 and GLUT1 in normal and wound healing conditions. However, in ODS rats, when compared with the AA-addition group, the formation of dentin bridges in the AA-loss group was not evident, a layer of osteopontin was significantly increased beneath the wound surface (p < 0.05), and alpha smooth muscle actin at the odontoblast-like cells observed along this layer was significantly increased (p < 0.05), but not Nestin. Moreover, the amounts of type 1 collagen generated in the reparative dentin and beneath the wound healing site were significantly diminished (p < 0.05). Macrophages expressing CD68 and CD206 increased beneath the wound site. Hence, AA may be involved in odontoblast-like cell differentiation and anti-inflammatory response during dental pulp wound healing. Our results provide new insights into the function of AA through SVCT2 and GLUT1 in reparative dentinogenesis and may help in developing new therapeutic targets for dental pulpal disease.
Topics: Rats; Animals; Rats, Wistar; Endothelial Cells; Dental Pulp; Glucose Transporter Type 1; Dentin, Secondary; Wound Healing; Odontoblasts; Sodium-Coupled Vitamin C Transporters; Ascorbic Acid
PubMed: 36690706
DOI: 10.1038/s41598-023-28197-9 -
TheScientificWorldJournal 2014In dental practice there is an increasing need for predictable therapeutic protocols able to regenerate tissues that, due to inflammatory or traumatic events, may suffer... (Review)
Review
In dental practice there is an increasing need for predictable therapeutic protocols able to regenerate tissues that, due to inflammatory or traumatic events, may suffer from loss of their function. One of the topics arising major interest in the research applied to regenerative medicine is represented by tissue engineering and, in particular, by stem cells. The study of stem cells in dentistry over the years has shown an exponential increase in literature. Adult mesenchymal stem cells have recently been isolated and characterized from tooth-related tissues and they might represent, in the near future, a new gold standard in the regeneration of all oral tissues. The aim of our review is to provide an overview on the topic reporting the current knowledge for each class of dental stem cells and to identify their potential clinical applications as therapeutic tool in various branches of dentistry.
Topics: Adult Stem Cells; Animals; Cells, Cultured; Dental Pulp; Dentistry; Humans; Mesenchymal Stem Cells; Odontoblasts; Osteoblasts; Regenerative Medicine; Tissue Engineering; Tooth
PubMed: 25379516
DOI: 10.1155/2014/151252