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The potential of obtaining cell cultures with neural crest resemblance (neural crest-derived stem cells [NCSCs]) from dental-related tissues, including human dental pulp cells (hDPCs), has been discussed in the literature. However, most reports include the use of serum-rich conditions and do not describe the potential for neural differentiation, slowing translation to the clinic. Therefore, we aimed to culture and characterize NCSCs from the human dental pulp in vitro and evaluate their ability to differentiate into neurons; we also investigated the effectiveness of the addition of BMP4 to enhance this potential. Cultures were established from a varied cohort of patient samples and grown, as monolayers, in serum, serum-free, and also under sphere-aggregation conditions to induce and identify a NCSC phenotype. hDPC cultures were characterized by immunocytochemistry and reverse transcription quantitative polymerase chain reaction. Monolayer cultures expressed stem cell, neural progenitor and neural crest-related markers. Culturing hDPCs as neurospheres (hDPC-NCSCs) resulted in an increased expression of neural crest-related genes, while the addition of BMP4 appeared to produce better NCSC characteristics and neural differentiation. The neural-like phenotype was evidenced by the expression of TUJ1, peripherin, NFH, TAU, SYN1, and GAP43. Our results describe the establishment of hDPC cultures from a large variety of patients in serum-free medium, as NCSC that differentiate into neural-like cells, as well as an important effect of BMP4 in enhancing the neural crest phenotype and differentiation of hDPCs., (© 2020 The Authors. STEM CELLS TRANSLATIONAL MEDICINE published by Wiley Periodicals LLC on behalf of AlphaMed Press.)

Introduction: Diabetes is a common disease that may have some influence on sensory nerves. The aim of this study was to evaluate dental pulp responses to 2 pulp sensibility tests (ie, cold and electric) in patients with type 2 diabetes compared with healthy individuals., Methods: Three hundred twenty-two premolar teeth in 51 patients who had type 2 diabetes and 347 premolar teeth in 53 individuals with no medical conditions were investigated. The patients with type 2 diabetes were unified and had fasting plasma glucose <300, hemoglobin A1C <10, less than a 10-year history of diabetes mellitus, and no history of hypertension. Electric and cold pulp sensibility tests were performed for all teeth. The cold test results were recorded by the Heft-Parker visual analog scale, and the electric pulp test results were recorded based on the pulp tester's grade that evoked a response., Results: There was no statistically significant difference between upper and lower premolar teeth in healthy individuals compared with the patients with diabetes in response to the cold and electric pulp tests (P > .05). In the patients with diabetes, the response of their upper premolars to the cold test was significantly reduced in diabetic patients >45 years of age (β = -1.15, P = .013). However, there was no significant correlation between the cold test and age in the lower premolars of both diabetic and nondiabetic participants (P > .05). There was also no significant correlation between the need for a higher number of the electric pulp test current to evoke a response in maxillary and mandibular premolars of the patients with diabetes and nondiabetic participants with age (P > .05)., Conclusions: There was a significant correlation between the reduction of maxillary premolar teeth responses to the cold test in diabetes patients >45 years of age., (Copyright © 2019 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)

Injury of the tooth pulp is excruciatingly painful and yet the receptors and neural circuit mechanisms that transmit this form of pain remain poorly defined in both the clinic and preclinical rodent models. Easily quantifiable behavioral assessment in the mouse orofacial area remains a major bottleneck in uncovering molecular mechanisms that govern inflammatory pain in the tooth. In this study we sought to address this problem using the Mouse Grimace Scale and a novel approach to the application of mechanical Von Frey hair stimuli. We use a dental pulp injury model that exposes the pulp to the outside environment, a procedure we have previously shown produces inflammation. Using RNAscope technology, we demonstrate an upregulation of genes that contribute to the pain state in the trigeminal ganglia of injured mice. We found that mice with dental pulp injury have greater Mouse Grimace Scores than sham within 24 hours of injury, suggestive of spontaneous pain. We developed a scoring system of mouse refusal to determine thresholds for mechanical stimulation of the face with Von Frey filaments. This method revealed that mice with a unilateral dental injury develop bilateral mechanical allodynia that is delayed relative to the onset of spontaneous pain. This work demonstrates that tooth pain can be quantified in freely behaving mice using approaches common for other types of pain assessment. Harnessing these assays in the orofacial area during gene manipulation should assist in uncovering mechanisms for tooth pulp inflammatory pain and other forms of trigeminal pain.

The tooth has an unusual sensory system that converts external stimuli predominantly into pain, yet its sensory afferents in teeth demonstrate cytochemical properties of non-nociceptive neurons. This review summarizes the recent knowledge underlying this paradoxical nociception, with a focus on the ion channels involved in tooth pain. The expression of temperature-sensitive ion channels has been extensively investigated because thermal stimulation often evokes tooth pain. However, temperature-sensitive ion channels cannot explain the sudden intense tooth pain evoked by innocuous temperatures or light air puffs, leading to the hydrodynamic theory emphasizing the microfluidic movement within the dentinal tubules for detection by mechanosensitive ion channels. Several mechanosensitive ion channels expressed in dental sensory systems have been suggested as key players in the hydrodynamic theory, and TRPM7, which is abundant in the odontoblasts, and recently discovered PIEZO receptors are promising candidates. Several ligand-gated ion channels and voltage-gated ion channels expressed in dental primary afferent neurons have been discussed in relation to their potential contribution to tooth pain. In addition, in recent years, there has been growing interest in the potential sensory role of odontoblasts; thus, the expression of ion channels in odontoblasts and their potential relation to tooth pain is also reviewed.

Introduction: To evaluate the stress at the apical third of the pulp and neurovascular bundle (NVB) during 5 types of orthodontic movement at different levels of bone loss. Furthermore, correlations among bone loss, orthodontic appliances, and stress increase were assessed., Methods: Based on cone-beam computed tomography datasets, 10 models of the mandibular second premolar were created. Each of these models was subjected to a gradual horizontal bone loss simulation (0-8 mm). Orthodontic forces of 20 g, 60 g, and 120 g were applied during the finite element analysis (FEA). For each bone loss level, stress values were evaluated with the use of Abaqus at the apical third of the pulp and the NVB., Results: The stress manifested at the apical third of the pulp was smaller than that at the NVB. The highest apical NVB stress was found for rotation (0.000546 N/mm 2 for 8 mm bone loss) whereas the lowest stress resulted after translational movements (2.35E-04 MPa for 8 mm bone loss). The FEA showed that Proffit's indicated orthodontic forces did not significantly disturb the pulpal blood flow and damage the apical NVB. Up to a doubling of the NVB stress, bone loss correlated with the force reduction to obtain similar stress levels compared with teeth with no bone loss., Conclusions: The present findings indicate that the stress manifested at the apical third of the pulp is smaller than that at NVB. Rotational movements induce the highest stress and translational forces develop the lowest stress related to the physiologic capillary blood pressure. Furthermore, in situations with reduced periodontium, lower forces are needed to reach the maximum tolerable stress compared with teeth with intact periodontium., (Copyright © 2019 American Association of Orthodontists. Published by Elsevier Inc. All rights reserved.)

This study further investigated the mechanisms underlying the rat model of tooth pulp inflammatory pain elicited by complete Freund's adjuvant (CFA), in comparison to other pulpitis models. Pulps of the left maxillary first molars were accessed. In the CFA group, the pulps were exposed, and CFA application was followed by dental sealing. In the open group, the pulps were left exposed to the oral cavity. For the closed group, the pulps were exposed, and the teeth were immediately sealed. Naïve rats were used as negative controls. Several parameters were evaluated at 1, 2, 3 and 8 days. There was no statistical significant difference among the groups when body weight variation, food or water consumption were compared. Analysis of serum cytokines (IL-1β, TNF or IL-6) or differential blood cell counts did not reveal any evidence of systemic inflammation. The CFA group displayed a significant reduction in the locomotor activity (at 1 and 3 days), associated with an increased activation of satellite glial cells in the ipsilateral trigeminal ganglion (TG; for up to 8 days). Amygdala astrocyte activation was unaffected in any experimental groups. We provide novel evidence indicating that CFA-induced pulp inflammation impaired the locomotor activity, with persistent activation of ipsilateral TG satellite cells surrounding sensory neurons, without any evidence of systemic inflammation or amygdala astrogliosis., Competing Interests: The authors have declared that no competing interests exist.

Successful disinfection alongside complete endodontic tissue regeneration and revascularization are the most desired clinical outcomes of regenerative endodontics. Despite reported clinical successes, significant limitations to the current regenerative endodontic procedure (REP) have been elucidated. To improve the current REP, an antibiotics and nitric oxide (NO) releasing biomimetic nanomatrix gel was developed. The study evaluates antibacterial effects of an antibiotics and NO releasing biomimetic nanomatrix gel on multispecies endodontic bacteria. Antibiotics, ciprofloxacin (CF) and metronidazole (MN) were mixed and encapsulated within the NO releasing biomimetic nanomatrix gel. The gel was synthesized and self-assembled from peptide amphiphiles containing various functional groups. Antibacterial effects of the antibiotics and NO releasing biomimetic nanomatrix gel were evaluated using bacterial viability assays involving endodontic microorganisms including clinical samples. Pulp-dentin regeneration was evaluated via animal-model experiments. The antibiotics and NO releasing biomimetic nanomatrix gel demonstrated a concentration dependent antibacterial effect. In addition, NO alone demonstrated a concentration dependent antibacterial effect on endodontic microorganism. An in vivo analysis demonstrated the antibiotics and NO releasing biomimetic nanomatrix gel promoted tooth revascularization with maturation of root canals. An optimal concentration of and NO releasing nanomatrix gel is suggested for its potential as a root treatment material for REP and an appropriate protocol for human trials. Further investigation is required to obtain a larger sample size and decide upon ideal growth factor incorporation., Competing Interests: The authors have declared that no competing interests exist.

In the context of tooth trauma, mostly the maxillary central front teeth are involved, whereby their roots are in some cases still in the developing stage (immature). Depending on the type of trauma, a necrosis of the pulp is the consequence or at least foreseeable. In order to preserve such a tooth, an endodontic therapy is inevitable. The disadvantage of conventional endodontic therapy methods of immature teeth (apexification, apexogenesis) is the root growth stop. Alternatively, the regeneration/revascularisation of the dental pulp (RP) was suggested, that allows a further root growth. The aim of this case report is to present the procedure of a RP-therapy and to suggest a step-by-step manual.

Objective: To investigate physical characteristics and behaviours of dental pulp cells of teeth isolated from a dentinogenesis imperfecta (DGI) patient with a novel dentin sialophosphoprotein (DSPP) mutation., Subjects and Methods: Whole exome and Sanger sequencing were employed to identify mutations. Physical characteristics of the teeth were examined. Pulp cells' behaviours including cell proliferation, colony-forming unit, osteogenic differentiation, pluripotent markers, and mesenchymal stem cell markers were investigated., Results: The proband had opalescent brown primary teeth with extensive loss of enamel. Mutation analysis revealed a novel heterozygous 4-bp deletion, c.1915&#95;1918delAAGT (p.K639QfsX674), in exon 5 of the DSPP associated with DGI. Analysis of the extracted primary incisor demonstrated a decrease in brightness but an increase in yellow and red chroma. The dentin showed reduced mineral density. The dentinal tubules were present in the predentin, but progressively collapsed in the dentin. The pulp cells exhibited markedly reduced CD105 expression, decreased cell proliferation, and smaller colony-forming units., Conclusions: We identified a novel mutation in the DSPP gene which disturbed dentin characteristics and pulp cells' behaviours. Our study expands the mutation spectrum and understanding of pathologic dentin phenotypes related to the frameshift deletion in the dentin phosphoprotein (DPP) region of the DSPP gene., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Introduction: In this retrospective study, we investigated long-term (over 3 years) follow-up results of teeth that exhibited contradictory results between the pulp sensibility test (thermal or electric pulp test) and ultrasound Doppler flowmetry (UDF) until 1 year after trauma to inspect the prognosis of the pulp., Methods: Data were collected from the records of trauma patients in our hospital between February 2012 and May 2015. The teeth that had continuously shown contrasting results on the pulp sensibility test and UDF until 1 year after trauma were chosen for the study. Cases with follow-up records of more than 3 years after trauma were finally included, and a retrospective chart review was performed., Results: Data from 343 teeth in 147 patients who visited the hospital with traumatic dental injuries were examined. Among these, 13 teeth from 7 patients were included, and the record of each case was reviewed. All the subjects showed negative responses on the pulp sensibility test and positive responses on UDF until 1 year after trauma. Ultimately, 8 of the 13 teeth recovered pulp sensibility. Two teeth failed to recover pulp sensibility and became symptomatic; root canal treatment was performed on the teeth. The remaining 3 teeth belonged to patients suffering from nerve damage; therefore, the pulp sensibility test was not feasible., Conclusions: Based on this study, UDF can be effectively used for the evaluation of pulpal status in traumatized teeth., (Copyright © 2017 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)

Aim: To investigate in human dental pulp fibroblasts (HDPF) the expression of factors involved in dental pulp physiopathological processes and in an experimental model of cell activation called nemosis, and to compare the behaviour of pulp cell activation with sound lung fibroblast MRC5, employed as a reference model for nemosis., Methodology: Nemotic response was induced in three-dimensional cultures of HDPF and lung fibroblasts. The expressions of molecules involved in physiological (alkaline phosphatase, type I collagen) and in inflammatory processes (IL-6, CXCL8, CCL20, COX-2) were studied using real-time PCR. Concentrations of IL-6 and CXCL8 were analysed during 4 days with ELISA. Nonparametric tests were used to determine statistical differences between groups., Results: A significant decrease (P < 0.001) in type I collagen and alkaline phosphatase was observed in MRC5 and HDPF nemotic responses. Although the amounts of mRNA differed between these cell types, there was an increase in CCL20, CXCL8 and COX-2 expression (P < 0.001). Unlike HDPF, MRC5 spheroids displayed significant amounts of IL-6 concentrations and mRNA expression. Notably, increased concentrations of CXCL8 were recorded in all three-dimensional cultures compared with monolayers as a function of time (P < 0.05)., Conclusion: Although the nemotic responses observed were not identical in the pulpal and lung fibroblasts, similarities occurred in the expression of chemokines and cyclooxygenase-2. Nemotic reactions and inflammatory processes in pulp diseases share similarities in terms of the expression of factors. Thus, this in vitro model could constitute a powerful tool to study intercellular relations within the dental pulp and to develop new local treatments to counteract the inflammatory reaction that occurs during pulpitis., (© 2017 International Endodontic Journal. Published by John Wiley & Sons Ltd.)

Background The mechanisms underlying tooth pulp hypersensitivity associated with masseter muscle hyperalgesia remain largely underinvestigated. In the present study, we aimed to determine whether masseter muscle contraction induced by daily electrical stimulation influences the mechanical head-withdrawal threshold and genioglossus electromyography activity caused by the application of capsaicin to the upper first molar tooth pulp. We further investigated whether astroglial glutamine synthesis is involved in first molar tooth pulp hypersensitivity associated with masseter muscle contraction. Methods The first molar tooth pulp was treated with capsaicin or vehicle in masseter muscle contraction or sham rats, following which the astroglial glutamine synthetase inhibitor methionine sulfoximine or Phosphate buffered saline (PBS) was applied. Astroglial activation was assessed via immunohistochemistry. Results The mechanical head-withdrawal threshold of the ipsilateral masseter muscle was significantly decreased in masseter muscle contraction rats than in sham rats. Genioglossus electromyography activity was significantly higher in masseter muscle contraction rats than sham rats. Glial fibrillary acidic protein-immunoreactive cell density was significantly higher in masseter muscle contraction rats than in sham rats. Administration of methionine sulfoximine induced no significant changes in the density of glial fibrillary acidic protein-immunoreactive cells relative to PBS treatment. However, mechanical head-withdrawal threshold was significantly higher in masseter muscle contraction rats than PBS-treated rats after methionine sulfoximine administration. Genioglossus electromyography activity following first molar tooth pulp capsaicin treatment was significantly lower in methionine sulfoximine-treated rats than in PBS-treated rats. In the ipsilateral region, the total number of phosphorylated extracellular signal-regulated protein kinase immunoreactive cells in the medullary dorsal horn was significantly smaller upon first molar tooth pulp capsaicin application in methionine sulfoximine-treated rats than in PBS-treated rats. Conclusions Our results suggest that masseter muscle contraction induces astroglial activation, and that this activation spreads from caudal to the obex in the medullary dorsal horn, resulting in enhanced neuronal excitability associated with astroglial glutamine synthesis in medullary dorsal horn neurons receiving inputs from the tooth pulp. These findings provide significant insight into the mechanisms underlying tooth pulp hypersensitivity associated with masseter muscle contraction.

The Purpose of the Study: determination of the optimal parameters of the action of various types of current, which have the most pronounced irritating effect on the receptor apparatus of the tooth pulp. The study involved 102 volunteers aged 19 to 72 years (53 females and 49 males). The study was conducted on 217 teeth: 86 molars, 25 premolars, 19 canines and 98 incisors. 137 (63%) teeth were intact, in 48 (22%) teeth caries were found, in 32 (15%) teeth there was pulpitis or teeth were depulpated. Electroexcitability of the teeth was determined with the help of various types of electric current: an impulse variable, an impulse constant and a sinusoidal variable. The optimal current for carrying out an electroodontodiagnosis proved to be sinusoidal variable current with a frequency of 50 Hz. This current does not cause polarization of tissues, it is easy to dose, it causes a clear, but not painful sensation, gives the smallest spread of the indicators during repeated studies. The obtained results allowed formulating requirements for electroodontodiagnosis devices.

The aim of the study was to investigate the effects of low-intensity pulsed ultrasound (LIPUS) on dentoalveolar structures during application of force to a cultured mandible slice taken from an ovariectomized rat model of osteoporosis. Rats were divided based on whether they had ovariectomy and/or LIPUS application into four groups: control osteoporosis group, control normal group, ultrasound-treated osteoporosis group and ultrasound-treated normal group. The mandibles were dissected, sliced and cultured before application of a 0.5-N force. Tissue specimens from five rats per group received LIPUS; the remaining rats served as untreated controls. Tissue sections were evaluated histologically and histomorphometrically. Osteoporosis significantly affected the alveolar bone without any effect on the dentin-pulp complex. LIPUS enhanced osteoporotic alveolar bone remodeling and increased cementum and predentin thickness. Furthermore, LIPUS application significantly increased odontoblast and periodontal ligament cell counts (p < 0.05) in both groups. Therefore, LIPUS enhances alveolar bone remolding and increases cementum and predentin formation in osteoporotic rat mandible slice organ cultures., (Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.)

Aim: To determine the prevalence of preoperative endodontic pain (PREP) and the incidence of postoperative endodontic pain (POEP), identifying the predictors of PREP and POEP in a southern Brazilian subpopulation, using clinical data from an electronic chart database (ECD)., Methodology: This retrospective observational study included 563 consecutive individuals presenting for root canal treatment (RCT). Patients were treated by undergraduate and graduate students, following standard RCT protocols. Demographic, medical and dental variables were extracted from a pre-structured and standardized ECD. The main outcomes PREP and incident POEP were collected through a 0-10 numeric rating scale, dichotomized as none/mild (<4) or moderate/severe (≥4) pain. Predictive models calculating the prevalence ratios (PR) of PREP and the relative risks (RR) of incident POEP were carried out with Poisson regression analysis, estimating the relationship between clinical factors, PREP and incident POEP., Results: Mean age at baseline was 49.2 ± 17.1 years, with 68.4% women. The prevalence and incidence of moderate/severe PREP and POEP were 44.4% and 3.8%, respectively. RCT intervention significantly reduced PREP (P < 0.001). Multivariate analysis revealed that group of teeth, location (mandibular teeth), pulpitis, necrotic pulp, preoperative swelling and periapical radiolucency were independently associated with moderate/severe PREP, whilst age ≥60 years and root canal retreatments were independent protective factors to PREP (P < 0.05). No demographic, medical or dental variables were associated with POEP, although molar teeth (RR = 4.23, 95%CI = 0.93-19.2, P = 0.056) had a borderline nonsignificant association., Conclusions: Moderate/severe PREP was independently associated with age, group of teeth, location, preoperative swelling, retreatments and pulp and periapical status. No demographic, medical or dental variable predicted moderate/severe POEP following RCT amongst this subpopulation., (© 2016 International Endodontic Journal. Published by John Wiley & Sons Ltd.)

Throughout lifetime, the teeth are continuously exposed to numerous chemical and physical impacts, which cause the wear of the dental hard tissues, gingival recession and other oral changes with sometimes subsequent problems. Age-related wear of tooth surfaces reduces the dental enamel thickness and exposes deeper layers of enamel, which have different physical and chemical properties than the surface enamel. Gingival recession is the main causal factor of root caries and dentine hypersensitivity. Age-related changes in dentine include the formation of secondary dentine and the reduction in tubular lumen diameter (dentine sclerosis), which lead to a reduction in the volume of the pulp chamber. In addition to the reduction in the volume of pulp chamber, changes to the dental pulp also include dental pulp calcifications. The age-related physiological changes to the teeth should be carefully distinguished from pathological changes, especially when they induce pain or a negative impact on the oral health-related quality of life (OHRQoL) of the older individuals. Therefore, regular oral examinations coupled with early preventive measures should aim at maintaining oral health until old age., (© 2016 John Wiley & Sons Ltd.)

Introduction: The purpose of this study was to ascertain the regenerative characteristics of apical papilla-derived cells (APDCs) from immature teeth with pulpal and periapical pathosis and thus to provide proof-of-principle evidence for further regenerative endodontic research., Methods: Pulpal and periapical pathosis was induced in immature permanent double-rooted premolars of beagles, which were randomly assigned to experimental treatment groups: group AO (n = 14), pulp disruption and access left open; group PS (n = 14), supragingival plaque suspension-soaked cotton pellet was introduced, and access was sealed; and control (n = 7), untreated. The teeth were extracted at 2- and 4-week periods after experimental treatments. APDCs were cultured from the extracted teeth, and their cellular proliferation, differentiation characteristics, and stemness were assessed. The data were statistically analyzed., Results: After 4 weeks of intentional pulpal and periapical pathosis induction period, all teeth in group PS showed features of apical periodontitis with necrotic pulp, and their APDCs showed significantly increased proliferation rate and osteogenic/odontogenic differentiation capabilities (P < .05). The stemness was maintained in all APDCs, although the stem cell population was smaller in group PS at 2-week period when the inflammatory responses were most fulminant (P < .05)., Conclusions: The APDCs from immature teeth retained the regenerative characteristics with the differences according to their pulpal and periapical pathosis. The results of this study partly provide the evidence for regenerative endodontic research., (Copyright © 2016 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)

Objective: To compare the proliferation and osteoblastic differentiation of dental pulp stem cell (DPSC) isolated from normal and inflamed pulps of different degrees in Beagle immature premolars, and provide evidence for the use of inflammatory DPSC (IDPSC)., Methods: This study evaluated 14 Beagle's young premolars (21 roots). In the experiment group, irreversible pulpitis was induced by pulp exposure and the inflamed pulps were extracted 2 weeks and 6 weeks after the pulp chamber opening.For the control group, normal pulps were extracted immediately after the exposure. HE staining and real-time PCR were performed to confirm the inflammation. The cells were isolated from the inflamed and normal pulps (IDPSC and DPSC). Cell proliferation and osteoblastic differentiation potentials of the two cells were compared., Results: Inflammation cells infiltration was observed in the inflamed pulps by HE staining. The expression of inflammatory factor was much higher in the 6 week inflamed pulp. IDPSC had higher potential of cell proliferation and osteoblastic differentiation potentials. Furthermore, the osteoblastic differentiation potentials of IDPSC from 2 week inflamed pulp were higher than those from 6 week inflamed pulp., Conclusion: The potential of cell proliferation and osteoblastic differentiation of DPSC was enhanced at early stage of irreversible pulpitis, and reduced at late stage in Beagle immature premolars.

Human dental pulp stem cells (DPSCs) can be isolated from inflamed pulp derived from carious teeth with symptomatic irreversible pulpitis (I-DPSCs), which possess stemness and multidifferentiation potentials similar to DPSCs from healthy pulp. Since macrophages-essential cell players of the pulpal innate immunity-can regulate pulpal inflammation and repair, the authors investigated the immunomodulatory effects of DPSCs/I-DPSCs on macrophage functions and their underlying mechanisms. Similar to DPSCs, I-DPSCs were capable of colony-forming efficiency and adipogenic and osteo/dentinogenic differentiation under in vitro induction conditions. I-DPSCs also expressed a similar phenotypic profile of mesenchymal stem cell markers, except a relatively higher level of CD146 as compared with DPSCs. Coculture of DPSCs or I-DPSCs with differentiated THP-1 cells, the human monocyte cell line, markedly suppressed tumor necrosis factor α (TNF-α) secretion in response to stimulation with lipopolysaccharides (LPS) and/or nigericin. However, unlike TNF-α, the secreted level of interleukin 1β was not affected by coculture with DPSCs or I-DPSCs. Furthermore, DPSC/I-DPSC-mediated inhibition of TNF-α secretion by macrophages was abolished by pretreatment with 1-methyl-D-tryptophan, a specific inhibitor of indoleamine-pyrrole 2,3-dioxygenase (IDO), but not by NSC-398, a specific inhibitor of COX-2, suggesting IDO as a mediator. Interestingly, IDO expression was significantly augmented in macrophages and mesenchymal stromal cells in inflamed human pulp tissues. Collectively, these findings show that I-DPSCs, similar to DPSCs, possess stem cell properties and suppress macrophage functions via the TNF-α/IDO axis, thereby providing a physiologically relevant context for their innate immunomodulatory activity in the dental pulp and their capability for pulp repair., Competing Interests: The authors declare no potential conflicts of interest with respect to the authorship and/or publication of this article., (© International & American Associations for Dental Research 2016.)

The anterograde intraflagellar transport motor protein, kif3a, regulates the integrity of primary cilia and various cellular functions, however, the role of kif3a in dental mesenchymal stem/precursor cell differentiation remains to be fully elucidated. In the present study, the expression of kif3a was knocked down in human dental follicle cells (hDFCs) and human dental pulp cells (hDPCs) using short hairpin RNA. The results of subsequent immunofluorescence revealed that knocking down kif3a resulted in the loss of primary cilia, which led to impairment of substantial mineralization and expression of the differentiation‑associated markers, including alkaline phosphatase, Runt‑related transcription factor 2, dentin matrix protein 1 and dentin sialophosphoprotein in the hDFCs and hDPCs. The results of reverse transcription‑quantitative polymerase chain reaction and western blot analyses showed that the expression levels of Wnt3a‑mediated active β‑catenin and lymphoid enhancer‑binding factor 1 were attenuated, whereas the expression of phosphorylated glycogen synthase kinase 3β was enhanced, in the kif3a‑knockdown cells. In addition, exogenous Wnt3a partially rescued osteoblastic differentiation in the hDFCs and hDPCs. These results demonstrated that inhibition of kif3a in the hDFCs and hDPCs disrupted primary cilia formation and/or function, and indicated that kif3a is important in the differentiation of hDFCs and hDPCs through the Wnt pathway. These findings not only enhance current understanding of tooth development and diseases of tooth mineralization, but also indicate possible strategies to regulate mineralization during tooth repair and regeneration.

Revascularization of immature teeth with necrotic pulps traditionally involves the use of triple antibiotic paste, which may sometimes lead to undesirable complications. The objective of this study was to assess tissue repair in immature dog teeth with apical periodontitis subjected to revascularization, comparing two different pastes used for root canal disinfection. Apical periodontitis was induced in 30 dog premolars. Teeth were randomly divided into three experimental groups: root canals filled with triple antibiotic paste (n = 10); root canals filled with 1% propolis paste (n = 10); and no medication (n = 10). An additional group (n = 10, no intervention) was used as control. After 7 months, the jaws were histologically evaluated for the following variables: newly formed mineralized tissue (present/absent); vital tissue in the canal space (absent/periodontal ligament-like/pulp-like); apical extension of root (present/absent); and severity of inflammatory process (absent/mild/moderate/severe). There were no statistically significant differences among the experimental groups in new mineralized tissue formation and apical root development. The formation of vital tissue in the canal space, in turn, was statistically different between the triple paste and propolis groups: vital tissues were present in all revascularized teeth disinfected with propolis paste (100%), compared to 71% of those disinfected with the triple paste. Severity of inflammatory process was different between the triple paste and no medication groups. The new tissues formed onto canal walls and in the root canal space showed characteristics of cementum and periodontal ligament, respectively. Propolis may have some advantages over the triple paste for the revascularization of immature teeth.

Aim: To investigate the inflammatory response of dental pulp fibroblasts and the respective explants to whole saliva., Methodology: Explants from human and porcine dental pulp tissue and isolated dental pulp fibroblasts were used to investigate the inflammatory response to sterile saliva. Cytokine and chemokine expression was assessed by RT-PCR. Western blot analysis and pharmacologic inhibitors were used to determine the involvement of signalling pathways., Results: Dental pulp explants of human and porcine origin exposed to human saliva exhibited no major changes of IL-6 and IL-8 mRNA expression (P > 0.05). In contrast, isolated porcine and human dental pulp fibroblasts, when stimulated with human saliva, exhibited a vastly increased expression of IL-6 and IL-8 mRNA (P < 0.05). In pulp fibroblasts, saliva also increased the expression of other cytokines and chemokines via activation of NFkappaB, ERK and p38 signalling. Notably, a significantly reduced inflammatory response was elicited when pulp fibroblasts were transiently exposed to saliva., Conclusions: Saliva has a potential impact on inflammation of dental pulp fibroblasts in vitro but not when cells are embedded in the intrinsic extracellular matrix of the explant tissue., (© 2015 International Endodontic Journal. Published by John Wiley & Sons Ltd.)

Introduction: Endodontic diagnostic tests are often used clinically to assess pulp status as a basis for the diagnosis and determination of whether root canal treatment (RCT) is indicated. Response to cold and pain on percussion are 2 common tests, yet their validity in identifying nonvital pulp in regular dental practice has not been reported., Methods: We assessed the validity of cold and percussion tests to identify nonvital pulp in teeth requiring RCT in a dental practice setting performed by 46 general dentists and 16 endodontists in the National Dental Practice-Based Research Network. The influence of patient-, tooth-, and dentist-related characteristics was investigated. Observed bleeding from the pulp chamber was the clinical reference. Sensitivity (SN), specificity (SP), overall test accuracy (TA), positive (PPV) and negative (NPV) predictive values, and likelihood and diagnostic odds ratios (LR+, LR-, dORs) were calculated for each single test and the combined cold and percussion tests., Results: Seven hundred eight patient teeth were included. Cold test showed high validity to identify a nonvital pulp status (SN = 89%, SP = 80%, TA = 84%, PPV = 81%, NPV = 88%, LR+ = 4.35, LR- = 0.14, dOR = 31.4), whereas pain on percussion had lower validity (SN = 72%, SP = 41%, TA = 56%, PPV = 54%, NPV = 60%, LR+ = 1.22, LR- = 0.69, dOR = 1.78). Combining the 2 tests did not increase validity, whereas preoperative pain, medication intake, patient age and sex, and dentist training level affected test validity significantly., Conclusions: In regular dental practice, the cold test exhibits higher validity to discriminate between vital and nonvital pulp than the tooth percussion test., (Copyright © 2016 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)

Life cycles of dental trauma victims can provide important clinical information, especially when viewed over many years. In this first series of life cycles, the pulp and periodontal responses to traumatic injuries of four patients are documented over periods varying from 26 to 51 years. The dynamics of pulp survival following an intrusive luxation and two avulsions are followed, with particular reference to pulp canal calcification to which a new term, root canal stenosis, has been proposed. The life cycles include the successful management of inflammatory root resorption in a replanted tooth with an open apex contrasting with the early prophylactic endodontic treatment of two replanted teeth in a patient with mature apices. The long-term development of invasive cervical resorption in one of the patient's life cycle highlights the importance of ongoing follow-up examinations for dental trauma victims., (© 2016 Australian Dental Association.)

For treating pulpal pathological conditions, pulpal regeneration through transplanted stem/progenitor cells might be an alternative to conventional root canal treatment. A number of animal studies demonstrated beneficial effects of stem/progenitor cell transplantation for pulp-dentin complex regeneration, that is, pulpal tissue, neural, vascular, and dentinal regeneration. We systematically reviewed animal studies investigating stem/progenitor cell-mediated pulp-dentin complex regeneration. Studies quantitatively comparing pulp-dentin complex regeneration after transplantation of stem/progenitor cells versus no stem/progenitor cell transplantation controls in intraoral in vivo teeth animal models were analyzed. The following outcomes were investigated: regenerated pulp area per root canal total area, capillaries per total surface, regenerated dentinal area per total defect area, and nerves per total surface. PubMed and EMBASE were screened for studies published until July 2014. Cross-referencing and hand searching were used to identify further articles. Standardized mean differences (SMD) and 95% confidence intervals (95% CI) were calculated using random-effects meta-analysis. To assess possible bias, SYRCLE's risk of bias tool for animal studies was used. From 1364 screened articles, five studies (representing 64 animals) were included in the quantitative analysis. Risk of bias of all studies was high. Stem/progenitor cell-transplanted pulps showed significantly larger regenerated pulp area per root canal total area (SMD [95% CI]: 2.28 [0.35-4.21]) and regenerated dentin area per root canal total area (SMD: 6.91 [5.39-8.43]) compared with no stem/progenitor cell transplantation controls. Only one study reported on capillaries per or nerves per total surface and found both significantly increased in stem/progenitor cell-transplanted pulps compared with controls. Stem/progenitor cell transplantation seems to enhance pulp-dentin complex regeneration in animal models. Due to limited data quantity and quality, current evidence levels are insufficient for further conclusions.

Objective: Assessing the pulp status plays a vital role in diagnosis and treatment planning in dentistry especially in children, who may not be able to verbalize their dental symptoms. Pulp sensibility test is used as a valuable investigation to evaluate the state of pulp. The aim of this study is to assess the efficiency and reliability of thermal and electrical pulp tests in primary teeth and to rule out the anxiety level involved in each tests., Study Design: 30 children aged between 6 to 8 years with carious primary molar teeth in need of conservative pulp therapy were included in this study. 3 tests at random were employed on each tooth which includes cold, heat, electrical pulp test. The sensitivity, specificity, positive predictive value and negative predictive value were evaluated based on the clinical visual examination on access opening and the accuracy for each test was calculated. The Facial Image Scale (FIS) was used to assess the state of dental anxiety in children due to these pulp sensibility tests., Results: The highest accuracy rate was calculated for EPT (0.814) followed by cold test (0.777) and heat test (0.759)., Conclusion: No significant association was found between the accuracy of all the three tests. (P value > 0.05). Cold test is the most reliable test due to its simplicity and ease to perform. (FIS -1.53).

Background: Accumulating clinical and preclinical evidence indicates that chronic pain is often comorbid with persistent low mood and anxiety. However, the mechanisms underlying pain-induced anxiety, such as its causality, temporal progression, and relevant neural networks are poorly understood, impeding the development of efficacious therapeutic approaches., Results: Here, we have identified the sequential emergence of anxiety phenotypes in mice subjected to dental pulp injury (DPI), a prototypical model of orofacial pain that correlates with human toothache. Compared with sham controls, mice subjected to DPI by mechanically exposing the pulp to the oral environment exhibited significant signs of anxiogenic effects, specifically, altered behaviors on the elevated plus maze (EPM), novelty-suppressed feeding (NSF) tests at 1 but not 3 days after the surgery. Notably, at 7 and 14 days, the DPI mice again avoided the open arm, center area, and novelty environment in the EPM, open field, and NSF tests, respectively. In particular, DPI-induced social phobia and increased repetitive grooming did not occur until 14 days after surgery, suggesting that DPI-induced social anxiety requires a long time. Moreover, oral administration of an anti-inflammatory drug, ibuprofen, or an analgesic agent, ProTx-II, which is a selective inhibitor of NaV1.7 sodium channels, both significantly alleviated DPI-induced avoidance in mice. Finally, to investigate the underlying central mechanisms, we pharmacologically blocked a popular form of synaptic plasticity with a GluA2-derived peptide, long-term depression, as that treatment significantly prevented the development of anxiety phenotype upon DPI., Conclusions: Together, these results suggest a temporally progressive causal relationship between orofacial pain and anxiety, calling for more in-depth mechanistic studies on concomitant pain and anxiety disorders.

The aim of this study was to evaluate the efficacy of different irrigation protocols, including laser, on the retention of the fiber-reinforced composite posts to root canal dentinal walls using pull-out tests. Root canals of 60 single-rooted human teeth were filled and post spaces were prepared. Finally, specimens were divided randomly into five groups, each consisting of 12 specimens as follows: 5% NaOCl (control group), 17% EDTA, ultrasonic with 17% EDTA, single 1.5-W Er:YAG laser application, and the combined use of Er:YAG laser and 17% EDTA. After the root canal procedures, fiber posts were cemented to the root canal. Pull-out tests were performed using a universal testing machine at a crosshead speed of 2 mm/min. The data were analyzed using a one-way ANOVA and Bonferroni post hoc test (p = 0.05). Irradiation by the Er:YAG laser with/without EDTA positively affected the pull-out bond strength (p < 0.001). The pull-out strength was significantly higher in the ultrasonic group than that of the single irrigation with NaOCl or EDTA (p < 0.001). Er:YAG laser irradiation with/without EDTA enhanced the bond strength of fiber posts to root canal dentin walls. Additionally, ultrasonic-EDTA combination increased the bond strength.

Dental pulp represents a specialized connective tissue enclosed by dentin and enamel, the most highly mineralized tissues of the body. Consequently, the direct examination as well as pathological evaluation of dental pulp is difficult. Within this anatomical context, our study aimed to evaluate the correlation between dental pulp lesions and clinical diagnosis. Pulpectomies were performed for 54 patients with acute and chronic irreversible pulpitides and for 5 patients (control group) with orthodontic extractions. The morphological features were semiquantitatively assessed by specific score values. The clinical and morphological correspondence was noted for 35 cases (68.62%), whereas inconsistency was recorded for 16 cases (31.38%). The results of the statistical analysis revealed the correlations between clinically and pathologically diagnosed acute/chronic pulpitides. No significant differences were established between the score values for inflammatory infiltrate intensity, collagen depositions, calcifications and necrosis, and acute, respectively chronic pulpitides. We also obtained significant differences between acute pulpitides and inflammatory infiltrate and calcifications and between chronic pulpitides and inflammatory infiltrate, collagen deposition, and calcifications. On the basis of the predominant pathological aspects, namely, acute and chronic pulpitis, we consider that the classification schemes can be simplified by adequately reducing the number of clinical entities.

Background: There is increasing evidence that peripheral glutamate signaling mechanism is involved in the nociceptive transmission during pathological conditions. However, little is known about the glutamate signaling mechanism and related specific type of vesicular glutamate transporter (VGLUT) in the dental pulp following inflammation. To address this issue, we investigated expression and protein levels of VGLUT1 and VGLUT2 in the dental pulp and trigeminal ganglion (TG) following complete Freund's adjuvant (CFA) application to the rat dental pulp by light microscopic immunohistochemistry and Western blot analysis., Results: The density of VGLUT2- immunopositive (+) axons in the dental pulp and the number of VGLUT2+ soma in the TG increased significantly in the CFA-treated group, compared to control group. The protein levels of VGLUT2 in the dental pulp and TG were also significantly higher in the CFA-treated group than control group by Western blot analysis. The density of VGLUT1+ axons in the dental pulp and soma in the TG remained unchanged in the CFA-treated group., Conclusions: These findings suggest that glutamate signaling that is mediated by VGLUT2 in the pulpal axons may be enhanced in the inflamed dental pulp, which may contribute to pulpal axon sensitization leading to hyperalgesia following inflammation.

Introduction: The purpose of this study was to investigate the effect of conditioned medium (CM) from murine preameloblasts on the cellular differentiation of mesenchymal stem cells (MSCs) in immature teeth with necrotic pulp and apical periodontitis., Methods: Pulp necrosis and apical periodontitis were induced in 30 immature permanent double-rooted premolars of 3 beagles and were randomly assigned to the following treatment groups: group CM (n = 10), revascularization treatment was performed using CM from preameloblasts of C57BL/6 mice apical bud cells; group CR (n = 10), conventional revascularization treatment was performed; positive control group (n = 5), left infected; and negative control group (n = 5), untreated. The dogs were followed up for 12 weeks and assessed for treatment outcomes with radiographic and histologic analyses. The effect of the CM on sequential Runx2 and osterix messenger RNA gene expression during the differentiation of MG63 osteoblastlike cells was analyzed with real-time polymerase chain reaction., Results: The overall treatment outcomes were not significantly different between the 2 treatment groups. However, the teeth in the CM group showed significantly more mature apices and a higher degree of hard tissue formation with projections intercalating into the pre-existing root dentin (P < .05). In CM-treated teeth, regenerated pulplike tissue was more frequently observed (P < .05). During differentiation, the CM induced early peak expression of Runx2 followed by sustained osterix overexpression., Conclusions: CM from preameloblasts rendered a favorable effect in providing a physiologic microenvironment for the differentiation of MSCs after revascularization treatment., (Copyright © 2014 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)

Introduction: This study evaluated the pulpal and periapical responses of dogs' teeth after pulpotomy and pulp capping with a new tricalcium silicate-based cement (Biodentine) when compared with mineral trioxide aggregate (MTA) by radiographic, histopathologic, and histomicrobiological analyses., Methods: Sixty roots (30 teeth) of dogs were divided into 2 groups, Biodentine (n = 36 roots) and ProRoot MTA (control, n = 24 roots). Animals were killed after 120 days, and the teeth were subjected to histotechnical processing (hematoxylin-eosin and Brown and Brenn staining). Qualitative and quantitative histopathologic data were analyzed by Fisher exact and Mann-Whitney tests (α = 0.05)., Results: Radiographically, mineralized tissue bridge formation was observed in more specimens treated with Biodentine (96.8%) than with MTA (72.2%) (P = .02). Integrity of the lamina dura and absence of periapical bone rarefaction and root resorption (external and internal) were observed in all specimens. Histopathologic and histomicrobiological analyses revealed mineralized tissue bridge formation, pulpal vitality, odontoblast layer integrity, preserved periodontal ligament, and absence of bone or root resorption and microorganisms in both groups. Although the bridges formed at the amputation site had similar morphology, they were significantly thicker in the Biodentine group (P < .0001). Comparison between the radiographic and histopathologic results showed that radiographic visualization of more bridges in the Biodentine group was related to bridge thickness because radiographic diagnosis was flawed for bridges with thickness less than 0.5 mm. Fluorescence microscopy improved the visualization of bridge structure., Conclusions: Biodentine presented tissue compatibility and allowed for mineralized tissue bridge formation after pulpotomy in all specimens with similar morphology and integrity to those formed with use of MTA. Periapical radiographs failed in detecting mineralized tissue bridges with thickness less than 0.5 mm., (Copyright © 2014 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)

Background: Traumatic tooth avulsions occur most often in 7 to 9 year-old children. Replantation is considered the treatment of choice and follow-up is required in order to prevent possible complications., Case Report: A case of replantation of a maxillary immature incisor in a 9.2-year-old male is reported. Tooth 21 was stored in saliva, in the child's mouth, and it was replanted within 45 min following a bicycle accident. A flexible splint was applied from tooth 11 to tooth 63, and it was removed after 4 weeks. Pulp canal obliteration was diagnosed at the 6 months check-up visit. Pulp sensibility was positive after 3 months and absent after 5 years. During the follow-up the tooth completed its development and always presented a physiological mobility and a probing depth <3 mm. Only a minimal discoloration of the crown was observed., Conclusion: The knowledge of emergency care at the scene of dental trauma is resolutory for treatment outcome.

Background: Extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein kinase are transiently phosphorylated (activated) in the spinal cord and trigeminal nucleus by acute noxious stimuli. Acute stimulation of dental pulp induces short-lived ERK activation in trigeminal subnucleus caudalis (Vc), and p38 inhibition attenuates short-term sensitization in Vc induced by acute pulpal stimulation. We have developed a model to study central changes following chronic inflammation of dental pulp that induces long-term sensitization. Here, we examine the effects of chronic inflammation and acute stimulation on the expression of phosphorylated ERK (pERK), phosphorylated p38 (pp38) and Fos in Vc., Results: Chronic inflammation alone induced bilateral expression of pERK and pp38 in Vc, but did not induce Fos expression. Stimulation of both non-inflamed and inflamed pulps significantly increased pERK and pp38 bilaterally; expression was greatest in inflamed, stimulated animals, and was similar following 10-min and 60-min stimulation. Stimulation for 60 min, but not 10 min, induced Fos in ipsilateral Vc; Fos expression was significantly greater in inflamed, stimulated animals. pERK was present in both neurons and astrocytes; pp38 was present in neurons and other non-neuronal, non-astrocytic cell types., Conclusions: This study provides the first demonstration that chronic inflammation of tooth pulp induces persistent bilateral activation of ERK and p38 within Vc, and that this activation is further increased by acute stimulation. This altered activity in intracellular signaling is likely to be linked to the sensitization that is seen in our animal model and in patients with pulpitis. Our data indicate that pERK and pp38 are more accurate markers of central change than Fos expression. In our model, localization of pERK and pp38 within specific cell types differs from that seen following acute stimulation. This may indicate specific roles for different cell types in the induction and maintenance of pulpitic and other types of pain., (Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background/aim: The assessment of pulp vitality is one of the major challenges in dental traumatology due to the temporary loss of sensibility after trauma and because of the limitations of conventional pulp tests. The aim of this study was to evaluate pulpal response to sensibility tests and to determine their accuracy after crown fractures and luxation injuries., Materials and Methods: A total of 121 permanent anterior teeth from 78 patients treated at the Dental Trauma Clinic of the Federal University of Minas Gerais were evaluated. Responses to pulp sensibility tests were monitored for a minimum period of 24 months or until the diagnosis of pulp necrosis., Results: At the first appointment, 68 teeth responded positively to sensibility tests, one tooth was necrotic and 52 teeth did not respond to sensibility tests but showed no other signs of necrosis. The initial lack of response was not associated with age (P = 0.18), but was related to the presence of luxation (P < 0.001). At the final appointment, 87 teeth were classified as vital and 31 were classified as non-vital. While a positive response shortly after trauma was a good predictor of vitality, a lack of response was not associated with subsequent necrosis. The final pulpal condition of the teeth that initially did not respond was associated with the type of injury, as displaced teeth tended to develop necrosis (P = 0.008). The accuracy of each sensibility test at the initial and final appointments was, respectively, 55.1% and 67.8% for the heat test, 55.9% and 77.9% for the cold test, and 57.6% and 89% for the electrical test., Conclusions: A temporary loss of sensibility was a frequent finding during post-traumatic pulpal healing, especially after luxation injuries. All sensibility tests presented low accuracy shortly after trauma. The electrical test provided the best support for pulpal diagnosis after long-term follow up. The clinician must be aware of additional signs of crown discoloration and radiographic changes before initiating endodontic treatment., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Functional magnetic resonance imaging (fMRI) has been widely used for investigating the brain representation associated with dental pain evoked by pulpal electrical stimulation. However, because of the heterogeneity of experimental designs and the small sample size of individual studies, the common brain representation regarding dental pain has remained elusive. We used imaging meta-analysis to investigate six dental pain-related fMRI studies (n = 87) and tested 3 hypotheses: (1) Dental pain is associated with the 'core' pain-related network; (2) pain-related brain activation is somatotopically organized in the somatosensory cortex; and (3) dental pain is associated with the cognitive-affective network related to pain. Qualitative and quantitative meta-analyses revealed: (1) common activation of the core pain-related network, including the somatosensory cortex, the insula, and the cingulate cortex; (2) inconsistency in somatotopically organized activation of the primary somatosensory cortex; and (3) common activation in the dorsolateral prefrontal cortex, suggesting a role of re-appraisal and coping in the experience of dental pain. In conclusion, fMRI combined with pulpal stimulation can effectively evoke activity in the pain-related network. The dental pain-related brain representation disclosed the mechanisms of how sensory and cognitive-affective factors shape dental pain, which will help in the development of more effective customized methods for central pain control.

Dental wear can be differentiated into different types on the basis of morphological and etiological factors. The present research was carried out on twelve extracted human teeth with dental wear (three teeth showing each type of wear: erosion, attrition, abrasion, and abfraction) studied by scanning electron microscopy (SEM). The study aimed, through analysis of the macro- and micromorphological features of the lesions (considering the enamel, dentin, enamel prisms, dentinal tubules, and pulp), to clarify the different clinical and diagnostic presentations of dental wear and their possible significance. Our results, which confirm current knowledge, provide a complete overview of the distinctive morphology of each lesion type. It is important to identify the type of dental wear lesion in order to recognize the contributing etiological factors and, consequently, identify other more complex, nondental disorders (such as gastroesophageal reflux, eating disorders). It is clear that each type of lesion has a specific morphology and mechanism, and further clinical studies are needed to clarify the etiological processes, particularly those underlying the onset of abfraction.

Aim: To describe the pattern of presentation of carious permanent teeth with pulp exposure and to determine factors associated with choice of treatment for such teeth., Materials and Methods: All patients presenting at the oral diagnosis clinic of Lagos University Teaching Hospital Dental centre between January 2009 and June 2009 were examined and those with carious lesion involving the pulp were included in the study. The history and character of pain from teeth, extent of tooth structure lost, proposed treatment and reason for proposed treatment was recorded., Results: The tooth most affected by pulp exposure due to caries is the lower first molar (17.5%). Extraction was the treatment of choice for many patients due to the following reasons: obliterated root canals (30%), patients' preference (30%) and non-restorable teeth (22%)., Conclusion: Extraction was the predominant treatment chosen for cariously exposed permanent teeth due to the condition of the tooth.

Introduction: Clinical regenerative endodontic treatment has been focused on immature necrotic teeth, but it should be extended to mature teeth as an alternative to conventional endodontic treatment. There have been no clinical reports to attempt to revascularize pulp in the entire root canals of mature necrotic teeth. The present report describes the treatment of mature, necrotic, permanent incisors with apical periodontitis by using regenerative endodontic therapy., Methods: In this case report, modified regenerative endodontic procedures were used to enhance the probability of pulp revasuclarization in mature necrotic teeth. At the first appointment, the root canals were mechanically instrumented to the apices with a large apical size by using the step-back technique and irrigated copiously with antimicrobial solution. Intracanal medicaments (calcium hydroxide or ciprofloxacin) were placed in the root canals. At the following appointment, the root canals were irrigated with antimicrobial solution, and bleeding was induced into the root canals by passing hand files beyond apices. Collagen membranes were placed in the canals as a matrix against which mineral trioxide aggregate was placed. Glass ionomer was used to restore the teeth. The resolution of apical radiolucency and regression of clinical signs and symptoms were observed at recall appointments., Conclusions: The present report presents modified regenerative endodontic procedures for mature necrotic permanent teeth. Further clinical studies with a large number of cases are needed to investigate the outcome of regenerative endodontic therapy for mature necrotic teeth., (Copyright © 2013 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)

Objective: To take the Real-time measurement of the intra-pulpal temperature (IPT) when using femtosecond laser in specific parameters to prepare cavities in tooth enamel in vitro, and to preliminarily evaluate the effect of air cooling., Methods: All pulp champers of extracted human teeth (premolars and molars) were exposed by roots amputated and pulp scraped out. All chambers were tightly filled with copper powder, and thermocouple was inserted into the center of the powder stack. The bottom of the chamber was sealed with insulating tape. Thermocouple wire was fixed at the same time. The 2.25 mm×2.25 mm square cavities were prepared using femtosecond laser in the enamel with the average scan speed of 0.4 mm/s. The real-time IPT change was measured with thermocouple digital thermometer. Air cooling was added to the procedure once the temperature increased to reach a balance., Results: The IPT rising was defined as ΔT . Before the usage of air cooling, the maximum of the ΔT value of the sample premolar was 12.3 °C. After using air cooling, the IPT decreased and ΔT value became 3.0 °C . The maximum of ΔT of the sample molar before using air cooling was 1.8 °C , and decreased to -0.1 °C after it., Conclusion: When preparing a cavity whose average depth is about 250 μm by femtosecond laser system in specific parameters, the IPT rises while the depth increass, but it could be controlled effectively by air cooling.

Introduction: Dental pulp functions include pulp cell activity involvement in dentin formation. In this study we investigated the age-related changes in dental pulp cells that may influence pulp cell activity for restoring pulp function., Methods: Human dental pulp cells (HDPCs) were serially subcultured until spontaneously arrested. Altered expression of chronic inflammatory molecules and age-related molecules were determined by Western blotting. Odontogenic functions impaired by senescence were assayed by Western blotting, reverse transcriptase polymerase chain reaction, alkaline phosphatase activity, and alizarin red S staining. To understand the mechanism of aging process by stress-induced premature senescence (SIPS), the cells were treated with H(2)O(2). Replicative senescence and SIPS were also compared., Results: Replicative senescence of HDPCs was characterized by senescence-associated β-galactosidase activity and reactive oxygen species formation. These cells exhibited altered expression of chronic inflammatory molecules such as intracellular adhesion molecule-1, vascular cell adhesion molecule-1, peroxisome proliferator activated receptor-gamma, and heme oxygenase-1 and age-related molecules such as p53, p21, phosphorylated-extracellular signal-regulated kinase, and c-myb. SIPS cell results were similar to replicative senescence. Furthermore, HDPCs decreased odontogenic markers such as dentin sialophosphoprotein and dentin matrix-1 and osteogenic markers such as bone morphogenetic protein-2 and -7, runt-related transcription factor-2, osteopontin, alkaline phosphatase activity, and mineralized nodule formation by replicative senescence and SIPS., Conclusions: This study suggests that development of aging-related molecules in pulp cells offers understanding of cellular mechanisms and biological events responsible for tooth preservation and maintenance strategies for healthy teeth across the life span., (Copyright © 2013 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)

Pain is associated with anxiety in a dental setting. It has remained unclear how cognitive-affective factors modulate pain and anxiety in a stressful context, such as receiving dental procedures. We hypothesized that both the situational factor (unpredictability about painful stimuli) and the trait factor (pain catastrophizing, i.e., the tendency to interpret pain in negative orientation) account for dental pain. Fifteen healthy participants were recruited to perform an associative learning task. They were asked to learn the pairing between visual cues and the intensity of incoming painful stimuli delivered at the right upper central incisor. Brain activation associated with pain was recorded by functional magnetic resonance imaging (fMRI). The participants reported increased anxiety and pain in the stressful context, where stimuli intensity was not predicted by the preceding cue. The score of the Pain Catastrophizing Scale was positively correlated with the increased pain modulated by unpredictability. Brain activation at the right posterior hippocampus, a region critically related to associative learning of aversive stimuli and context, was correlated with the individual catastrophizing level. Our findings suggest that both the situational factor (unpredictability) and the trait factor (catastrophizing) influence dental pain, highlighting the role of cognitive-affective factors in pain control of dental patients.

Diagnosis and treatment for traumatic dental injuries are very complex owing to the multiple trauma entities represented by six luxation types and nine fracture types affecting both the primary and the permanent dentition. When it is further considered that fracture and luxation injuries are often combined, the result is that more than 100 trauma scenarios exist, when the two dentitions are combined. Each of these trauma scenarios has a specific treatment demand and prospect for healing. With such a complexity in diagnosis and treatment, it is obvious that even experienced practitioners may have problems in selecting proper treatment for some of these trauma types. To remedy this situation, an Internet-based knowledge base consisting of 4000 dental trauma cases with long-term follow up is now available to the public and the professions on the Internet using the address http://www.DentalTraumaGuide.org. It is the aspiration that the use of this Guide may lead the practitioner to offer an evidence-based diagnosis and treatment., (© 2012 John Wiley & Sons A/S.)

Regenerative endodontics has encountered substantial challenges toward clinical translation. The adoption by the American Dental Association of evoked pulp bleeding in immature permanent teeth is an important step for regenerative endodontics. However, there is no regenerative therapy for most endodontic diseases. Simple recapitulation of cell therapy and tissue engineering strategies that are under development for other organ systems has not led to clinical translation in regeneration endodontics. Recent work using novel biomaterial scaffolds and growth factors that orchestrate the homing of host endogenous cells represents a departure from traditional cell transplantation approaches and may accelerate clinical translation., (Copyright © 2012 Elsevier Inc. All rights reserved.)

The management of a tooth with incomplete root maturation and a necrotic pulp is an endodontic and a restorative challenge. Apexification procedures alone leave the tooth in a weakened state and at risk for reinfection. Regenerative endodontic procedures potentially offer advantages, including the possibility of hard tissue deposition and continued root development. Case studies have reported regeneration of human pulplike tissues in vivo, but there is no protocol that reliably regenerates pulplike tissue. This article summarizes historical, current, and future regenerative treatment approaches., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Introduction: Mutations in the gene ALPL in hypophosphatasia (HPP) reduce the function of tissue nonspecific alkaline phosphatase, and the resulting increase in pyrophosphate (PP(i)) contributes to bone and tooth mineralization defects by inhibiting physiologic calcium-phosphate (P(i)) precipitation. Although periodontal phenotypes are well documented, pulp/dentin abnormalities have been suggested in the clinical literature although reports are variable and underlying mechanisms remains unclear. In vitro analyses were used to identify mechanisms involved in HPP-associated pulp/dentin phenotypes., Methods: Primary pulp cells cultured from HPP subjects were established to assay alkaline phosphatase (ALP) activity, mineralization, and gene expression compared with cells from healthy controls. Exogenous P(i) was provided to the correct P(i)/PP(i) ratio in cell culture., Results: HPP cells exhibited significantly reduced ALP activity (by 50%) and mineral nodule formation (by 60%) compared with the controls. The expression of PP(i) regulatory genes was altered in HPP pulp cells, including reduction in the progressive ankylosis gene (ANKH) and increased ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1). Odontoblast marker gene expression was disrupted in HPP cells, including reduced osteopontin (OPN), dentin matrix protein 1 (DMP1), dentin sialophosphoprotein (DSPP), and matrix extracellular phosphoprotein (MEPE). The addition of P(i) provided a corrective measure for mineralization and partially rescued the expression of some genes although cells retained altered messenger RNA levels for PP(i)-associated genes., Conclusions: These studies suggest that under HPP conditions pulp cells have the compromised ability to mineralize and feature a disrupted odontoblast profile, providing a first step toward understanding the molecular mechanisms for dentin phenotypes observed in HPP., (Published by Elsevier Inc.)

The work performed by researchers in regenerative endodontics and tissue engineering over the last decades has been superb; however, many questions remain to be answered. The basic biologic mechanisms must be elucidated that will allow the development of dental pulp and dentin in situ. Stress must be placed on the many questions that will lead to the design of effective, safe treatment options and therapies. This article discusses those questions, the answers to which may become the future of regenerative endodontics. The future remains bright, but proper support and patience are required., (Copyright © 2012 Elsevier Inc. All rights reserved.)

The pulp-dentin complex is a strategic and dynamic barrier to various insults that plague the dentition. Researchers have yet to understand the complete potential of this shifting junction and its components. The most common cause of injury to the pulp-dentin complex is carious breakdown of enamel and dentin. In recent years, there has been a change in restorative management of caries. The emphasis is on strategies to preserve dentin and protect the pulp. This article provides a brief review of the effect of caries on the pulp, of subsequent events on the periradicular tissues, and of current understanding of treatment modalities., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Introduction: The purpose of this study was to compare the anesthetic efficacy of 0.5% bupivacaine with 1:200,000 epinephrine with that of 2% lidocaine with 1:100,000 epinephrine during pulpectomy in patients with irreversible pulpitis in mandibular posterior teeth., Methods: Seventy volunteers, patients with irreversible pulpitis admitted to the Emergency Center of the School of Dentistry at the University of São Paulo, randomly received a conventional inferior alveolar nerve block containing 3.6 mL of either 0.5% bupivacaine with 1:200,000 epinephrine or 2% lidocaine with 1:100,000 epinephrine. During the subsequent pulpectomy, we recorded the patients' subjective assessments of lip anesthesia, the absence/presence of pulpal anesthesia through electric pulp stimulation, and the absence/presence of pain through a verbal analog scale., Results: All patients reported lip anesthesia after the application of either inferior alveolar nerve block. By measuring pulpal anesthesia success with the pulp tester, lidocaine had a higher success rate (42.9%) than bupivacaine (20%). For patients reporting none or mild pain during pulpectomy, the success rate of bupivacaine was 80% and lidocaine was 62.9%. There were only statistically significant differences to the success of pulpal anesthesia., Conclusions: Neither of the solutions resulted in an effective pain control during irreversible pulpitis treatments of mandibular molars., (Copyright © 2012 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)

Introduction: To assess, in vivo, the influence of periodontal attachment loss and gingival recession on responses to pulp sensibility tests (PSTs) with cold stimuli in mandibular incisors in adult patients., Methods: This cross-sectional study included 45 patients aged 30 to 60 years treated at a university dental health service. In each patient, 1 mandibular incisor was randomly selected for analysis. One calibrated dentist performed all periodontal assessments. Periodontal attachment loss and gingival recession were measured at 6 sites of the selected tooth followed by application of the PST on the buccal surface of the tooth by an independent operator. Each patient was asked to indicate a score for pain intensity on a numeric visual analog scale. The Pearson correlation coefficient was used to investigate and quantify the correlation between predictor variables (periodontal attachment loss and gingival recession) and reported pain. Simple and multiple linear regression analyses were performed to determine the impact of periodontal attachment loss and gingival recession on PST pain scores., Results: Multivariate analysis showed that periodontal attachment loss contributed significantly to the prediction of pain in response to the PST (P < .001). Increases of 1 mm in periodontal attachment loss resulted in a decrease of approximately 0.5 score on the pain scale. Gingival recession also contributed as a predictor of the outcome (P < .001) with a decrease of approximately 0.7 in pain scores for every 1-mm increase in gingival recession. The correlations were in the opposite direction than expected., Conclusions: Periodontal attachment loss and gingival recession strongly influenced reported pain in response to PST with cold stimuli. The effect of both variables was constant (ie, responses to PST decreased gradually with increases in periodontal attachment loss and gingival recession)., (Copyright © 2012 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.)