Wnt signalling in oral and maxillofacial diseases.

Wnts include more than 19 types of secreted glycoproteins that are involved in a wide range of pathological processes in oral and maxillofacial diseases. The transmission of Wnt signalling from the extracellular matrix into the nucleus includes canonical pathways and noncanonical pathways, which play an important role in tooth development, alveolar bone regeneration, and related diseases. In recent years, with the in-depth study of Wnt signalling in oral and maxillofacial-related diseases, many new conclusions and perspectives have been reached, and there are also some controversies. This article aims to summarise the roles of Wnt signalling in various oral diseases, including periodontitis, dental pulp disease, jaw disease, cleft palate, and abnormal tooth development, to provide researchers with a better and more comprehensive understanding of Wnts in oral and maxillofacial diseases.

Ubiquitination and Deubiquitination in Oral Disease.

Oral health is an integral part of the general health and well-being of individuals. The presence of oral disease is potentially indicative of a number of systemic diseases and may contribute to their early diagnosis and treatment. The ubiquitin (Ub) system has been shown to play a role in cellular immune response, cellular development, and programmed cell death. Ubiquitination is a post-translational modification that occurs in eukaryotes. Its mechanism involves a number of factors, including Ub-activating enzymes, Ub-conjugating enzymes, and Ub protein ligases. Deubiquitinating enzymes, which are proteases that reversely modify proteins by removing Ub or Ub-like molecules or remodeling Ub chains on target proteins, have recently been regarded as crucial regulators of ubiquitination-mediated degradation and are known to significantly affect cellular pathways, a number of biological processes, DNA damage response, and DNA repair pathways. Research has increasingly shown evidence of the relationship between ubiquitination, deubiquitination, and oral disease. This review investigates recent progress in discoveries in diseased oral sites and discusses the roles of ubiquitination and deubiquitination in oral disease.

The role of biomineralization in disorders of skeletal development and tooth formation.

The major mineralized tissues are bone and teeth, which share several mechanisms governing their development and mineralization. This crossover includes the hormones that regulate circulating calcium and phosphate concentrations, and the genes that regulate the differentiation and transdifferentiation of cells. In developing endochondral bone and in developing teeth, parathyroid hormone-related protein (PTHrP) acts in chondrocytes to delay terminal differentiation, thereby increasing the pool of precursor cells. Chondrocytes and (in specific circumstances) pre-odontoblasts can also transdifferentiate into osteoblasts. Moreover, bone and teeth share outcomes when affected by systemic disorders of mineral homeostasis or of the extracellular matrix, and by adverse effects of treatments such as bisphosphonates and fluoride. Unlike bone, teeth have more permanent effects from systemic disorders because they are not remodelled after they are formed. This Review discusses the normal processes of bone and tooth development, followed by disorders that have effects on both bone and teeth, versus disorders that have effects in one without affecting the other. The takeaway message is that bone specialists should know when to screen for dental disorders, just as dental specialists should recognize when a tooth disorder should raise suspicions about a possible underlying bone disorder.

Protein-Based Salivary Profiles as Novel Biomarkers for Oral Diseases.

The Global Burden of Oral Diseases affects 3.5 billion people worldwide, representing the number of people affected by the burden of untreated dental caries, severe periodontal disease, and edentulism. Thus, much more efforts in terms of diagnostics and treatments must be provided in the fight of these outcomes. In this sense, recently, the study of saliva as biological matrix has been identified as a new landmark initiative in the search of novel and useful biomarkers to prevent and diagnose these conditions. Specifically, saliva is a rich reservoir of different proteins and peptides and accessible due to recent advances in molecular biology and specially in targeted and unbiased proteomics technologies. Nonetheless, emerging barriers are an obstacle to the study of the salivary proteome in an effective way. This review aims at giving an overall perspective of salivary biomarkers identified in several oral diseases by means of molecular biology approaches.

Generation and Role of Reactive Oxygen and Nitrogen Species Induced by Plasma, Lasers, Chemical Agents, and Other Systems in Dentistry.

The generation of reactive oxygen and nitrogen species (RONS) has been found to occur during inflammatory procedures, during cell ischemia, and in various crucial developmental processes such as cell differentiation and along cell signaling pathways. The most common sources of intracellular RONS are the mitochondrial electron transport system, NADH oxidase, and cytochrome P450. In this review, we analyzed the extracellular and intracellular sources of reactive species, their cell signaling pathways, the mechanisms of action, and their positive and negative effects in the dental field. In dentistry, ROS can be found-in lasers, photosensitizers, bleaching agents, cold plasma, and even resin cements, all of which contribute to the generation and prevalence of ROS. Nonthermal plasma has been used as a source of ROS for biomedical applications and has the potential for use with dental stem cells as well. There are different types of dental stem cells, but their therapeutic use remains largely untapped, with the focus currently on only periodontal ligament stem cells. More research is necessary in this area, including studies about ROS mechanisms with dental cells, along with the utilization of reactive species in redox medicine. Such studies will help to provide successful treatment modalities for various diseases.

DENTAL ENAMEL FORMATION AND IMPLICATIONS FOR ORAL HEALTH AND DISEASE.

Dental enamel is the hardest and most mineralized tissue in extinct and extant vertebrate species and provides maximum durability that allows teeth to function as weapons and/or tools as well as for food processing. Enamel development and mineralization is an intricate process tightly regulated by cells of the enamel organ called ameloblasts. These heavily polarized cells form a monolayer around the developing enamel tissue and move as a single forming front in specified directions as they lay down a proteinaceous matrix that serves as a template for crystal growth. Ameloblasts maintain intercellular connections creating a semi-permeable barrier that at one end (basal/proximal) receives nutrients and ions from blood vessels, and at the opposite end (secretory/apical/distal) forms extracellular crystals within specified pH conditions. In this unique environment, ameloblasts orchestrate crystal growth via multiple cellular activities including modulating the transport of minerals and ions, pH regulation, proteolysis, and endocytosis. In many vertebrates, the bulk of the enamel tissue volume is first formed and subsequently mineralized by these same cells as they retransform their morphology and function. Cell death by apoptosis and regression are the fates of many ameloblasts following enamel maturation, and what cells remain of the enamel organ are shed during tooth eruption, or are incorporated into the tooth's epithelial attachment to the oral gingiva. In this review, we examine key aspects of dental enamel formation, from its developmental genesis to the ever-increasing wealth of data on the mechanisms mediating ionic transport, as well as the clinical outcomes resulting from abnormal ameloblast function.

Status of Serum and Salivary Levels of Superoxide Dismutase in Type 2 Diabetes Mellitus with Oral Manifestations: A Case Control Study.

BACKGROUND: Type 2 Diabetes Mellitus is a very well known metabolic disorder that has reached epidemic proportions worldwide. Evidence suggests that oxidative stress increases in Diabetes Mellitus because of the excessive production of reactive oxygen species and an impaired antioxidant defence mechanism. This study estimated, compared and correlated the serum and salivary Superoxide dismutase levels in healthy subjects and subjects with Type 2 Diabetes Mellitus having oral manifestations. MATERIALS AND METHODS: In this study, serum and salivary Superoxide dismutase levels were estimated in 45 healthy subjects and 45 patients with Type 2 Diabetes Mellitus with oral manifestations. RESULTS: The mean serum and salivary Superoxide dismutase levels were significantly decreased in subjects with Type 2 Diabetes Mellitus with oral manifestations compared to the healthy subjects. Positive correlation in both healthy and diabetics was observed between serum and salivary samples. CONCLUSION: This study highlights that the abnormally high levels of oxidative stress in diabetics coupled with simultaneous decline in antioxidant defence mechanism results in complications in Diabetes mellitus. Thus exploring saliva for antioxidant markers that accurately reflect the redox status of the body is worthwhile.

Biomarkers in the dentin-pulp complex: role in health and disease.

Biomarkers are functional elements at the cellular or molecular level, playing important roles in health and disease. The dentin-pulp complex of the tooth houses several biomarkers at different stages of development, and a lack of these biomarkers results in developmental disorders. Furthermore, biomarkers play a very important role in the pathogenesis of dental caries, pulpal and periapical pathoses in two ways - they are essential elements in the pathological process and their detection helps in accurate diagnosis of the pathological condition. The aim of this paper is to review the literature regarding the important biomarkers involved in the development of the dentin-pulp complex and in the pathological conditions involving the dentin-pulp complex.

Involvement of trigeminal transition zone and laminated subnucleus caudalis in masseter muscle hypersensitivity associated with tooth inflammation.

A rat model of pulpitis/periapical periodontitis was used to study mechanisms underlying extraterritorial enhancement of masseter response associated with tooth inflammation. Periapical bone loss gradually increased and peaked at 6 weeks after complete Freund's adjuvant (CFA) application to the upper molar tooth pulp (M1). On day 3, the number of Fos-immunoreactive (IR) cells was significantly larger in M1 CFA rats compared with M1 vehicle (veh) rats in the trigeminal subnucleus interpolaris/caudalis transition zone (Vi/Vc). The number of Fos-IR cells was significantly larger in M1 CFA and masseter (Mass) capsaicin applied (M1 CFA/Mass cap) rats compared with M1 veh/Mass veh rats in the contralateral Vc and Vi/Vc. The number of phosphorylated extracellular signal-regulated kinase (pERK)-IR cells was significantly larger in M1 CFA/Mass cap and M1 veh/Mass cap rats compared to Mass-vehicle applied rats with M1 vehicle or CFA in the Vi/Vc. Pulpal CFA application caused significant increase in the number of Fos-IR cells in the Vi/Vc but not Vc on week 6. The number of pERK-IR cells was significantly lager in the rats with capsaicin application to the Mass compared to Mass-vehicle treated rats after pulpal CFA- or vehicle-application. However, capsaicin application to the Mass did not further affect the number of Fos-IR cells in the Vi/Vc in pulpal CFA-applied rats. The digastric electromyographic (d-EMG) activity after Mass-capsaicin application was significantly increased on day 3 and lasted longer at 6 weeks after pulpal CFA application, and these increase and duration were significantly attenuated by i.t. PD98059, a MEK1 inhibitor. These findings suggest that Vi/Vc and Vc neuronal excitation is involved in the facilitation of extraterritorial hyperalgesia for Mass primed with periapical periodontitis or acute pulpal-inflammation. Furthermore, phosphorylation of ERK in the Vi/Vc and Vc play pivotal roles in masseter hyperalgesia after pulpitis or periapical periodontitis.

[Disorders of the stomatognathic system in patients with short stature]. / Zaburzenia ukladu stomatognatycznego u osób z niskorosloscia.

Growth hormone (GH) is a polypeptide hormone produced by the cells of pituitary. Production of growth hormone is carried out in a pulsating manner, and the frequency and intensity of the pulses is dependent on age and gender. Growth hormone deficiency (GHD) is characterized by, among others, slow growth process often from early childhood, delayed bone age. The aim of the study was to describe dental problems of children with short stature with a special attention on disorders at the craniofacial region such as decreased growth of maxilla and mandible, gnathic and bite dysfunctions, delayed teeth eruption, tooth caries susceptibility. Growth hormone treatment undertaken at the right time significantly influences on correct development of cranial bones and dentition, and supports orthodontic treatment.

Chemical characterization of etched dentin in non-carious cervical lesions.

PURPOSE: Bonding to non-carious cervical lesion (NCCL) sclerotic dentin that involves acid etching continues to be a challenging problem due to its altered chemical structure. In the present study, the objective was to investigate the chemical response of NCCL sclerotic dentin to the different acid etching times. MATERIALS AND METHODS: Extracted human premolars affected with NCCLs were selected, and a cavity matching the natural lesion with respect to size and location was prepared on the lingual surface of each tooth to serve as the control. The dentin surfaces were treated for 15 s and 30 s using 37% phosphoric acid and then analyzed by Raman microspectroscopic mapping/imaging. RESULTS: NCCL dentin substrates had dramatic effects on the chemical profile of dentin demineralization. The spectral comparison showed that the demineralized layer generated by the acid treatment was highly irregular in terms of depth and mineral component retained, especially when NCCL sclerotic dentin was etched for 15 s. When the etching time was increased to 30 s, the demineralization of NCCL sclerotic dentin was more effective and comparable to the nonsclerotic control that was treated for 15 s. Different etching times affected the depth, degree, and profile of the dentin demineralization. CONCLUSION: The shorter etching time (ie, 15 s) might not be adequate for NCCL sclerotic dentin. However, the longer etching time (ie, 30 s) would induce much deeper demineralized dentin for nonsclerotic substrates. Thus, although extended etching times can be used to remove the hypermineralized layer, further studies are required to analyze the impact this might have on the dentin bonding.

[Effect of harmful chemical air impurities on some parameters of the oral cavity].

The paper describes guidelines for studying the role of harmful chemical air impurities at work in the development of diseases of the teeth and periodontium, by applying the nonparametric methods that can substantiate conclusions on the nature and mechanism of a cause-and-effect relation when the number of observations is limited.

Effect of kallikrein 4 loss on enamel mineralization: comparison with mice lacking matrix metalloproteinase 20.

Enamel formation depends on a triad of tissue-specific matrix proteins (amelogenin, ameloblastin, and enamelin) to help initiate and stabilize progressively elongating, thin mineral ribbons of hydroxyapatite formed during an appositional growth phase. Subsequently, these proteins are eradicated to facilitate lateral expansion of the hydroxyapatite crystallites. The purpose of this study was to investigate changes in enamel mineralization occurring in mice unable to produce kallikrein 4 (Klk4), a proteinase associated with terminal extracellular degradation of matrix proteins during the maturation stage. Mice lacking functional matrix metalloproteinase 20 (Mmp20), a proteinase associated with early cleavage of matrix proteins during the secretory stage, were also analyzed as a frame of reference. The results indicated that mice lacking Klk4 produce enamel that is normal in thickness and overall organization in terms of layers and rod/inter-rod structure, but there is a developmental defect in enamel rods where they first form near the dentinoenamel junction. Mineralization is normal up to early maturation after which the enamel both retains and gains additional proteins and is unable to mature beyond 85% mineral by weight. The outmost enamel is hard, but inner regions are soft and contain much more protein than normal. The rate of mineral acquisition overall is lower by 25%. Mice lacking functional Mmp20 produce enamel that is thin and structurally abnormal. Relatively high amounts of protein remain throughout maturation, but the enamel is able to change from 67 to 75% mineral by weight during maturation. These findings reaffirm the importance of secreted proteinases to enamel mineral acquisition.

Oral diseases: from detection to diagnostics.

In addition to saliva, other oral components such as gingival crevicular fluid, epithelial cells, bacteria, breath, and dental plaque have diagnostic potential. For oral diseases such as caries and periodontal disease, visual diagnosis is usually adequate, but objective diagnostic tests with predictive value are desired. Therefore, prediction models like the Cariogram have been developed that also include oral aspects such as saliva secretion, buffering capacity, and Streptococcus mutans counts for the prediction of caries. Correlation studies on salivary components and caries have not been conclusive, but correlation studies on functional aspects, such as saliva-induced bacterial aggregation and caries, look promising. Modern proteomic techniques make it possible to study simultaneously the many salivary components involved in these functions.

Neuroendocrine cells in the dental pulp in health and disease.

Neuroendocrine cells were identified in human dental pulp by immunohistochemical method using monoclonal antibodies. A population of neuroendocrine cells positively reacting to neuron-specific enolase, synaptophysin, chromogranin A, and stained with paraldehyde-fuchsin, was detected in the subodontoblastic layer of the pulp. Changes in their count, morphology, and function in caries and pulpitis concomitant with periodontitis were proven.

Alveolar bone Sharpey fibers of the rat incisor in normal and altered functional conditions examined by scanning electron microscopy.

The morphology and the area density of Sharpey fibers in the socket of the rat incisor under normo-, hyper-, and hypofunctional conditions were evaluated using scanning electron microscopy. Sharpey fibers appeared either as dome-shaped projections, when highly mineralized, or as depressions when less mineralized. Near the alveolar crest, most of the fibers were fully mineralized and arranged in compact longitudinal rows. Toward the basal end of the socket, the rows became interrupted, forming islets of gradually smaller size and number. The density of the Sharpey fibers was higher (P < 0.01) in the mesial and distal faces than in the lingual face in most of the socket length. In normofunctional conditions, in all faces the density decreased 70 to 90 times from the crestal toward the basal region of the socket (P < 0.01). The degree of mineralization of the Sharpey fibers also decreased steadily in the same direction, indicating that, for support, the periodontal ligament matures from basal to incisal and is fully developed only in the crestal region. In hyper- and hypofunctional conditions, the same distribution was observed. The area density of the Sharpey fibers in the hyperfunctional condition showed a slight increase at the basal levels of the socket mesial and distal faces (P < 0.01 or P < 0.05). In hypofunctional incisors, the density decreased significantly (P < 0.01) at the mesial and distal faces in all regions of the socket, and at the lingual face, the decrease (P < 0.05) was restricted to the incisal regions. This may be one of the factors for the weakening of the periodontal ligament in hypofunctional incisors.

Comparison of fluorine level in the tissues of healthy teeth and teeth with decay process.

The aim of the study was to examine quantitative fluorine content in tooth tissues with the decay process, tissues of teeth without decay and tissues with diseases different than those of decay origin. It has been found that in the examined teeth decay process the average fluorine content in hard tissues amounted to 235.6 ppm of fluorine and it was lower than in healthy teeth (304.8 ppm) extracted for orthodontic or periodontological reasons, whereas the highest fluorine content--383.5 ppm--was found in teeth with diseases of non-decay etiology. Analyzing particular teeth groups depending on the age of the patients, it was observed that the fluorine level is higher in the teeth received from younger patients, especially in the group of healthy teeth and teeth with wedge defects. Susceptibility of tooth enamel to dissolution was estimated by the CRT test with the use of discs impregnated with crystal violet (hexamethylene-4 hydrochloride of fuchsin) with the range of colour change from yellow and green to violet and blue at ph 0.1-1.5. The lengthening of the time of reaction in this test testified to lower acid sensitivity of tissues and at the same time to harder demineralization of enamel, e.g. in the process of decay. Longer time of reaction was observed in teeth with higher indicated fluorine content.

Prospects for applying fluorescence spectroscopy to diagnose the hard tissues of a tooth.

This article deals with the autofluorescence spectra from the hard tissues of a tooth, both in norm and pathology. An investigation was made on 30 extracted human teeth. The measurements were made both for the intact hard tissues of a tooth, such as enamel, dentine, cementum, and root canal, and for the tissues pathologically affected by a caries (superficial, intermediate, and deep) and by a dental calculus. It was found that the fluorescent spectra from enamel, dentine, cementum, and from the regions affected by a caries and dental calculus were identical in form. All the spectra revealed a maximum near 700 nm. However, the intact and affected hard tissues were greatly different in the integral fluorescent intensity. Dental calculus was found to produce the most pronounced fluorescent intensity, whereas the carious regions produced a slightly weaker fluorescent intensity. On the contrary, the intact hard tissues of a tooth exhibited the poorest fluorescent intensity.

The increase of formaldehyde level in some rare pathological cases of teeth determined with the use of quantitative TLC.

In our previous works we proved that formaldehyde (HCHO) level in hard tissues of teeth could depend on their physiological state. In the current paper we presented the results of HCHO determinations in different dental pathologies, mainly the ones rarely encountered in dental practice, e.g. in the case of reinclusion. The determination of HCHO in the form of dimedone was performed by means of quantitative TLC. The obtained results were compared with HCHO levels in hard tissues of teeth presenting pathological changes. It proved that the highest HCHO level was found in reincluded teeth while it was lower in retained teeth, that is the ones which are not subjected to stress factors present in the mouth. The obtained results can constitute a contribution to the problems of dental pathologies, mainly caries which is a very common problem.

Comparative quantitative chromatographic determination of formaldehyde in different groups of physiological and pathological hard tissues of teeth.

Taking into consideration that HCHO level in cells of plant, animal and human tissues as well as in body fluids depends from physiological state of an organism in the current study it was decided to find out if there are changes of HCHO level in different physiological and pathological hard tissues of teeth. The obtained results showed in all 4 groups of teeth separately analysed that there were some regularities in the level of HCHO as far as similar physiological or pathological states are concerned. This was best seen when comparing the obtained results with mean HCHO level of the studied groups of teeth.