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Anatomical Record (Hoboken, N.J. : 2007) Sep 2022Patterns of genetic variation and covariation impact the evolution of the craniofacial complex and contribute to clinically significant malocclusions in modern human...
Patterns of genetic variation and covariation impact the evolution of the craniofacial complex and contribute to clinically significant malocclusions in modern human populations. Previous quantitative genetic studies have estimated the heritabilities and genetic correlations of skeletal and dental traits in humans and nonhuman primates, but none have estimated these quantitative genetic parameters across the dentognathic complex. A large and powerful pedigree from the Jirel population of Nepal was leveraged to estimate heritabilities and genetic correlations in 62 maxillary and mandibular arch dimensions, incisor and canine lengths, and post-canine tooth crown areas (N ≥ 739). Quantitative genetic parameter estimation was performed using maximum likelihood-based variance decomposition. Residual heritability estimates were significant for all traits, ranging from 0.269 to 0.898. Genetic correlations were positive for all trait pairs. Principal components analyses of the phenotypic and genetic correlation matrices indicate an overall size effect across all measurements on the first principal component. Additional principal components demonstrate positive relationships between post-canine tooth crown areas and arch lengths and negative relationships between post-canine tooth crown areas and arch widths, and between arch lengths and arch widths. Based on these findings, morphological variation in the human dentognathic complex may be constrained by genetic relationships between dental dimensions and arch lengths, with weaker genetic correlations between these traits and arch widths allowing for variation in arch shape. The patterns identified are expected to have impacted the evolution of the dentognathic complex and its genetic architecture as well as the prevalence of dental crowding in modern human populations.
Topics: Animals; Dental Arch; Humans; Likelihood Functions; Malocclusion; Maxilla; Nepal; Tooth Crown
PubMed: 34981668
DOI: 10.1002/ar.24857 -
Journal of Dental Research Dec 2014Stemming from in vitro and in vivo pre-clinical and human models, tissue-engineering-based strategies continue to demonstrate great potential for the regeneration of the... (Review)
Review
Stemming from in vitro and in vivo pre-clinical and human models, tissue-engineering-based strategies continue to demonstrate great potential for the regeneration of the pulp-dentin complex, particularly in necrotic, immature permanent teeth. Nanofibrous scaffolds, which closely resemble the native extracellular matrix, have been successfully synthesized by various techniques, including but not limited to electrospinning. A common goal in scaffold synthesis has been the notion of promoting cell guidance through the careful design and use of a collection of biochemical and physical cues capable of governing and stimulating specific events at the cellular and tissue levels. The latest advances in processing technologies allow for the fabrication of scaffolds where selected bioactive molecules can be delivered locally, thus increasing the possibilities for clinical success. Though electrospun scaffolds have not yet been tested in vivo in either human or animal pulpless models in immature permanent teeth, recent studies have highlighted their regenerative potential both from an in vitro and in vivo (i.e., subcutaneous model) standpoint. Possible applications for these bioactive scaffolds continue to evolve, with significant prospects related to the regeneration of both dentin and pulp tissue and, more recently, to root canal disinfection. Nonetheless, no single implantable scaffold can consistently guide the coordinated growth and development of the multiple tissue types involved in the functional regeneration of the pulp-dentin complex. The purpose of this review is to provide a comprehensive perspective on the latest discoveries related to the use of scaffolds and/or stem cells in regenerative endodontics. The authors focused this review on bioactive nanofibrous scaffolds, injectable scaffolds and stem cells, and pre-clinical findings using stem-cell-based strategies. These topics are discussed in detail in an attempt to provide future direction and to shed light on their potential translation to clinical settings.
Topics: Animals; Dental Pulp; Dentin; Humans; Prosthesis Design; Regeneration; Root Canal Therapy; Stem Cells; Tissue Engineering; Tissue Scaffolds
PubMed: 25201917
DOI: 10.1177/0022034514549809 -
Anatomical Record (Hoboken, N.J. : 2007) Dec 2021Tooth plates are a unique dental organ found in holocephalan fishes and lungfish. The chimaeroid tooth plates are atypical in terms of biomineralization, due to the hard...
Tooth plates are a unique dental organ found in holocephalan fishes and lungfish. The chimaeroid tooth plates are atypical in terms of biomineralization, due to the hard tissue composition of whitlockite and apatite, while those of lungfish and other vertebrates are composed of apatite. The tooth plates are overlaid by a thin veneer-outer dentin-whose composition and role are not known. We aimed to test whether the outer dentin is composed of whitlockite or apatite, and whether it protects the osteodentin from abrasion and supports its overall strength. For this purpose, the mineral components and microstructure of outer dentin were studied. Our analyses of the outer dentin from the anterior (vomerine) tooth plates of Chimaera phantasma revealed that the mineral component is magnesium- and carbonate-containing calcium-deficient apatite and that the outer dentin has a three-zone structure. The main body is sandwiched between thin zones, which are less mineralized than the main body. Furthermore, in the outer zone and the main body, a higher-order structure was formed in accordance with the organization of wide and narrow fibers. Mineralization made the main body a composite of bundles of fibers and apatite. Transmission electron microscopy showed a structural relationship between apatite and the fibrous component on which the apatite was formed. Such a structure of the main body could be highly effective as a framework to resist abrasion and support the overall strength of the tooth plate.
Topics: Animals; Apatites; Dentin; Fishes; Minerals; Tooth
PubMed: 33620142
DOI: 10.1002/ar.24606 -
Biomolecules Feb 2022The aim of this systematic review was to evaluate the application of potential therapeutic signaling molecules on complete dentin-pulp complex and pulp tissue... (Review)
Review
The aim of this systematic review was to evaluate the application of potential therapeutic signaling molecules on complete dentin-pulp complex and pulp tissue regeneration in orthotopic and ectopic animal studies. A search strategy was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement in the MEDLINE/PubMed database. Animal studies evaluating the application of signaling molecules to pulpectomized teeth for pulp tissue or dentin-pulp complex regeneration were included. From 2530 identified records, 18 fulfilled the eligibility criteria and were subjected to detailed qualitative analysis. Among the applied molecules, basic fibroblast growth factor, vascular endothelial growth factor, bone morphogenetic factor-7, nerve growth factor, and platelet-derived growth factor were the most frequently studied. The clinical, radiographical and histological outcome measures included healing of periapical lesions, root development, and apical closure, cellular recolonization of the pulp space, ingrowth of pulp-like connective tissue (vascularization and innervation), mineralized dentin-like tissue formation along the internal dentin walls, and odontoblast-like cells in contact with the internal dentin walls. The results indicate that signaling molecules play an important role in dentin/pulp regeneration. However, further studies are needed to determine a more specific subset combination of molecules to achieve greater efficiency towards the desired tissue engineering applications.
Topics: Animals; Dental Pulp; Dentin; Regeneration; Tissue Engineering; Vascular Endothelial Growth Factor A
PubMed: 35204786
DOI: 10.3390/biom12020285 -
Journal of Dental Research Feb 2018The importance of phosphate (Pi) as an essential component of hydroxyapatite crystals suggests a key role for membrane proteins controlling Pi uptake during...
The importance of phosphate (Pi) as an essential component of hydroxyapatite crystals suggests a key role for membrane proteins controlling Pi uptake during mineralization in the tooth. To clarify the involvement of the currently known Pi transporters (Slc17a1, Slc34a1, Slc34a2, Slc34a3, Slc20a1, Slc20a2, and Xpr1) during tooth development and mineralization, we determined their spatiotemporal expression in murine tooth germs from embryonic day 14.5 to postnatal day 15 and in human dental samples from Nolla stages 6 to 9. Using real-time polymerase chain reaction, in situ hybridization, immunohistochemistry, and X-gal staining, we showed that the expression of Slc17a1, Slc34a1, and Slc34a3 in tooth germs from C57BL/6 mice were very low. In contrast, Slc34a2, Slc20a1, Slc20a2, and Xpr1 were highly expressed, mostly during the postnatal stages. The expression of Slc20a2 was 2- to 10-fold higher than the other transporters. Comparable results were obtained in human tooth germs. In mice, Slc34a2 and Slc20a1 were predominantly expressed in ameloblasts but not odontoblasts, while Slc20a2 was detected neither in ameloblasts nor in odontoblasts. Rather, Slc20a2 was highly expressed in the stratum intermedium and the subodontoblastic cell layer. Although Slc20a2 knockout mice did not show enamel defects, mutant mice showed a disrupted dentin mineralization, displaying unmerged calcospherites at the mineralization front. This latter phenotypical finding raises the possibility that Slc20a2 may play an indirect role in regulating the extracellular Pi availability for mineralizing cells rather than a direct role in mediating Pi transport through mineralizing plasma cell membranes. By documenting the spatiotemporal expression of Pi transporters in the tooth, our data support the possibility that the currently known Pi transporters may be dispensable for the initiation of dental mineralization and may rather be involved later during the tooth mineralization scheme.
Topics: Animals; Female; France; Humans; Immunohistochemistry; In Situ Hybridization; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Phosphate Transport Proteins; Real-Time Polymerase Chain Reaction; Tooth Calcification; Tooth Germ; X-Ray Microtomography; Xenotropic and Polytropic Retrovirus Receptor
PubMed: 28892649
DOI: 10.1177/0022034517729811 -
Prague Medical Report 2018The effect of the nervous system on bone remodelling has been described by many studies. Sensory and autonomic nerves are present in the bone. Immunohistochemical... (Review)
Review
The effect of the nervous system on bone remodelling has been described by many studies. Sensory and autonomic nerves are present in the bone. Immunohistochemical analysis of the bone have indicated the presence of neuropeptides and neurotransmitters that act on bone cells through receptors. Besides carrying sensory information, sensory neurons produce various neuropeptides playing an important role in maintaining bone and tooth pulp homeostasis, and dentin formation. Bone tissue and teeth contain organic and inorganic components. Bone cells enable bone mineralization and ensure its formation and resorption. Studies focused on the effects of the nervous system on the bone are proceeded using various ways. Sensory denervation itself can be achieved using capsaicin causing chemical lesion to the nerve. Surgical ways of causing only sensory lesion to nerves are substantially limited because many peripheral nerves are mixed and contain a motor component as well. From this point of view, the experimental model with transection of inferior alveolar nerve is appropriate. This nerve provides sensory innervation of the bone and teeth of the mandible. The purpose of our paper is to provide an overview of the effects exerted by the nervous system on the inorganic component of the bone and teeth, and also to present an overview of the used experimental models. As we assume, the transection of inferior alveolar nerve could be reflected in changed contents and distribution of chemical elements in the bone and teeth of rat mandible. This issue has not been studied so far.
Topics: Animals; Denervation; Dental Pulp; Neurons, Afferent; Rats; Tooth
PubMed: 30779698
DOI: 10.14712/23362936.2019.1 -
European Cells & Materials Nov 2021Matrix metalloproteinases (MMPs) have been implicated not only in the regulation of developmental processes but also in the release of biologically active molecules and... (Review)
Review
Matrix metalloproteinases (MMPs) have been implicated not only in the regulation of developmental processes but also in the release of biologically active molecules and in the modulation of repair during tertiary dentine formation. Although efforts to preserve dentine have focused on inhibiting the activity of these proteases, their function is much more complex and necessary for dentine repair than expected. The present review explores the role of MMPs as bioactive components of the dentine matrix involved in dentine formation, repair and regeneration. Special consideration is given to the mechanical properties of dentine, including those of reactionary and reparative dentine, and the known roles of MMPs in their formation. MMPs are critical components of the dentine matrix and should be considered as important candidates in dentine regeneration.
Topics: Dentin; Dentin, Secondary; Humans; Matrix Metalloproteinases
PubMed: 34818431
DOI: 10.22203/eCM.v042a24 -
Tissue Engineering. Part B, Reviews Aug 2022The recent discovery of mesenchymal stem cells within periapical lesions (PL-MSC) has presented novel opportunities for managing periradicular diseases in adult teeth by... (Review)
Review
The recent discovery of mesenchymal stem cells within periapical lesions (PL-MSC) has presented novel opportunities for managing periradicular diseases in adult teeth by way of enhancing tissue regeneration. This discovery coincides with the current paradigm shift toward biologically driven treatment strategies in endodontics, which have typically been reserved for non-vital immature permanent teeth. One such approach that shows promise is utilizing local endogenous non-collagenous dentine extracellular matrix components (dECM) to recruit and upregulate the intrinsic regenerative capacity of PL-MSCs . At picogram levels, these morphogens have demonstrated tremendous ability to enhance the cellular activities in and animal studies that would otherwise be necessary for periradicular regeneration. Briefly, these include proliferation, viability, migration, differentiation, and mineralization. Therefore, topical application of dECMs during ortho- or retrograde root canal treatment could potentially enhance and sustain the regenerative mechanisms within diseased periapical tissues that are responsible for attaining favorable clinical and radiographic outcomes. This would provide many advantages when compared with conventional antimicrobial-only therapies for apical periodontitis (AP), which do not directly stimulate healing and have had stagnant success rates over the past five decades despite significant advances in operative techniques. The aim of this narrative review was to present the novel concept of exploiting endogenous dECMs as clinical tools for treating AP in mature permanent teeth. A large scope of literature was summarized to discuss the issues associated with conventional treatment modalities; current knowledge surrounding PL-MSCs; composition of the dECM; inductive potentials of dECM morphogens in other odontogenic stem cell niches; how treatment protocols can be adapted to take advantage of dECMs and PL-MSCs; and finally, the challenges currently impeding successful clinical translation alongside directions for future research. Impact statement Apical periodontitis (AP) is an inflammatory condition that is associated with a great degree of morbidity and ultimately leads to tooth loss. The purpose of this review was to summarize the current evidence pertaining to stem cell therapy in endodontics and present a novel clinical methodology through which they may be utilized to address AP. A comprehensive overview of the basic science, clinical translation, and potential challenges are presented in this review.
Topics: Animals; Cell Differentiation; Dentin; Periapical Periodontitis; Root Canal Therapy; Tissue Engineering
PubMed: 34309453
DOI: 10.1089/ten.TEB.2021.0074 -
Journal of Dental Research Apr 2017The acquired enamel pellicle is an oral, fluid-derived protein layer that forms on the tooth surface. It is a biologically and clinically important integument that...
The acquired enamel pellicle is an oral, fluid-derived protein layer that forms on the tooth surface. It is a biologically and clinically important integument that protects teeth against enamel demineralization, and abrasion. Tooth surfaces are exposed to different proteinaceous microenvironments depending on the enamel location. For instance, tooth surfaces close to the gingival sulcus contact serum proteins that emanate via this sulcus, which may impact pellicle composition locally. The aims of this study were to define the major salivary and serum components that adsorb to hydroxyapatite, to study competition among them, and to obtain preliminary evidence in an in vivo saliva/serum pellicle model. Hydroxyapatite powder was incubated with saliva and serum, and the proteins that adsorbed were identified by mass spectrometry. To study competition, saliva and serum proteins were labeled with CyDyes, mixed in various proportions, and incubated with hydroxyapatite. In vivo competition was assessed using a split-mouth design, with half the buccal tooth surfaces coated with serum and the other half with saliva. After exposure to the oral environment for 0 min, 30 min and 2 h, the pellicles were analyzed by SDS-PAGE. In pure saliva- or serum-derived pellicles, 82 and 84 proteins were identified, respectively. When present concomitantly, salivary protein adsorbers effectively competed with serum protein adsorbers for the hydroxyapatite surface. Specifically, acidic proline-rich protein, cystatin, statherin and protein S100-A9 proteins competed off apolipoproteins, complement C4-A, haptoglobin, transthyretin and serotransferrin. In vivo evidence further supported the replacement of serum proteins by salivary proteins. In conclusion, although significant numbers of serum proteins emanate from the gingival sulcus, their ability to participate in dental pellicle formation is likely reduced in the presence of strong salivary protein adsorbers. The functional properties of the acquired enamel pellicle will therefore be mostly dictated by the salivary component.
Topics: Adsorption; Biofilms; Blood Proteins; Chromatography, Liquid; Dental Enamel; Dental Pellicle; Durapatite; Humans; Male; Mass Spectrometry; Proteomics; Saliva; Salivary Proteins and Peptides; Surface Properties
PubMed: 27879420
DOI: 10.1177/0022034516680771 -
Matrix Biology : Journal of the... 2016Dental enamel is the hardest tissue in the human body, and although it starts as a tissue rich in proteins, by the time of eruption of the tooth in the oral cavity only... (Review)
Review
Dental enamel is the hardest tissue in the human body, and although it starts as a tissue rich in proteins, by the time of eruption of the tooth in the oral cavity only a small fraction of the protein remains. While this organic matrix of enamel represents less than 1% by weight it plays essential roles in improving both toughness and resilience to chemical attacks. Despite the fact that the first studies of the enamel matrix began in the 19th century, its exact composition and mechanisms of its function remain poorly understood. It was proposed that keratin or a keratin-like primitive epithelial component exists in mature enamel, however due to the extreme insolubility of its organic matrix the presence of keratins there was never clearly established. We have recently identified expression of a number of hair keratins in ameloblasts, the enamel secreting cells, and demonstrated their incorporation into mature enamel. Mutation in epithelial hair keratin KRT75 leads to a skin condition called pseudofollicularis barbae. Carriers of this mutation have an altered enamel structure and mechanical properties. Importantly, these individuals have a much higher prevalence of caries. To the best of our knowledge, this is the first study showing a direct link between a mutation in a protein-coding region of a gene and increased caries rates. In this paper we present an overview of the evidence of keratin-like material in enamel that has accumulated over the last 150years. Furthermore, we propose potential mechanisms of action of KTR75 in enamel and highlight the clinical implications of the link between mutations in KRT75 and caries. Finally, we discuss the potential use of keratins for enamel repair.
Topics: Animals; Dental Caries; Dental Enamel; Hair Diseases; Humans; Keratins, Hair-Specific; Keratins, Type II; Mutation
PubMed: 26709044
DOI: 10.1016/j.matbio.2015.12.007