Motoneurons that innervate the jaw-closing and jaw-opening muscles play a critical role in oro-facial behaviors, including mastication, suckling, and swallowing. These motoneurons can alter their physiological properties through the postnatal period during which feeding behavior shifts from suckling to mastication; however, the functional synaptic properties of developmental changes in these neurons remain unknown. Thus, we explored the postnatal changes in glutamatergic synaptic transmission onto the motoneurons that innervate the jaw-closing and jaw-opening musculatures during early postnatal development in rats. We measured miniature excitatory postsynaptic currents (mEPSCs) mediated by non-NMDA receptors (non-NMDA mEPSCs) and NMDA receptors in the masseter and digastric motoneurons. The amplitude, frequency, and rise time of non-NMDA mEPSCs remained unchanged among postnatal day (P)2-5, P9-12, and P14-17 age groups in masseter motoneurons, whereas the decay time dramatically decreased with age. The properties of the NMDA mEPSCs were more predominant at P2-5 masseter motoneurons, followed by reduction as neurons matured. The decay time of NMDA mEPSCs of masseter motoneurons also shortened remarkably across development. Furthermore, the proportion of NMDA/non-NMDA EPSCs induced in response to the electrical stimulation of the supratrigeminal region was quite high in P2-5 masseter motoneurons, and then decreased toward P14-17. In contrast to masseter motoneurons, digastric motoneurons showed unchanged properties in non-NMDA and NMDA EPSCs throughout postnatal development. Our results suggest that the developmental patterns of non-NMDA and NMDA receptor-mediated inputs vary among jaw-closing and jaw-opening motoneurons, possibly related to distinct roles of respective motoneurons in postnatal development of feeding behavior.

No abstract available

Trigeminal motoneurons (MNs) innervating the jaw-closing and jaw-opening muscles receive numerous inhibitory synaptic inputs from GABAergic and glycinergic neurons, which are essential for oromotor functions, such as the orofacial reflex, suckling, and mastication. The properties of the GABAergic and glycinergic inputs of these MNs undergo developmental alterations during the period in which their feeding behavior proceeds from suckling to mastication; however, the detailed characteristics of the developmental patterns of GABAergic and glycinergic transmission in these neurons remain to be elucidated. This study was conducted to investigate developmental changes in miniature inhibitory postsynaptic currents (mIPSCs) in masseter (jaw-closing) and digastric (jaw-opening) MNs using brainstem slice preparations obtained from Wistar rats on postnatal day (P)2-5, P9-12, and P14-17. The frequency and amplitude of glycinergic mIPSCs substantially increased with age in both the masseter and digastric MNs. The rise time and decay time of glycinergic mIPSCs in both MNs decreased during development. In contrast, the frequency of GABAergic components in masseter MNs was higher at P2-5 than at P14-17, whereas that in the digastric MNs remained unchanged throughout the postnatal period. The proportion of currents mediated by GABA-glycine co-transmission was higher at P2-5, and then it decreased with age in both MNs. These results suggest that characteristics related to the development of inhibitory synaptic inputs differ between jaw-closing and jaw-opening MNs and between GABAergic and glycinergic currents. These distinct developmental characteristics may contribute to the development of feeding behaviors.

Hyperparathyroidism-jaw tumor syndrome is a rare autosomal dominant disease characterized by parathyroid tumors and ossifying fibroma of the jaw. Disease-causing mutations have been localized in the tumor suppressor gene CDC73. This study is designed to highlight the importance of genetic testing in the diagnosis of ossifying fibroma related to this syndrome.

Jaw dystonia and laryngospasm in the context of subacute brainstem dysfunction have been described in a small number of diseases, including antineuronal nuclear antibody type 2 (ANNA-2, also known as anti-Ri) paraneoplastic neurologic syndrome. Severe episodes of laryngospasms causing cyanosis are potentially fatal. Jaw dystonia can also cause eating difficulty, resulting in severe weight loss and malnutrition. In this report, we highlight the multidisciplinary management of this syndrome associated with ANNA-2/anti-Ri paraneoplastic neurologic syndrome and discuss its pathogenesis.

The human jaw muscles are essential to mastication and play an important part in craniofacial growth. They contribute to dental and articular forces, deform the mandible, and, like other tissues, are subject to disorders, often manifested as pain. The literature describes how their contraction is controlled by the nervous system, and how their general structure and function contribute to craniofacial biology, but there has been little appraisal of their internal organization. Most of these muscles are not simple; they are multipennate, complexly layered, and divided by aponeuroses. This arrangement provides substantial means for differential contraction. In many ways, jaw muscle fibers are intrinsically dissimilar from those found in other skeletal muscles, because they are arranged in homogeneous clusters and generally reveal type I or type II histochemical profiles. Most are type I and are distributed preferentially in the anterior and deeper parts of the jaw closers. Additionally, most motor unit (MU) territories are smaller than those in the limbs. There is circumstantial evidence for intramuscular partitioning based in part on innervation by primary muscle nerve branches. During normal function. MU recruitment and the rate coding of MU firing in human jaw muscles follow the general principles established for the limbs, but even here they differ in important respects. Jaw muscle MUs do not have stable force recruitment thresholds and seem to rely more on rate coding than on sequential unit recruitment to grade the amplitude of muscle contraction. Unlike those in the limbs, their twitch tensions correlate weakly with MU fatiguability and contraction speed, probably because there are so few slow, fatigue-resistant MUs in the jaw muscles. Moreover, the type I fibers that are present in such large numbers do not contract as slowly as normally expected. To complicate matters, estimation of jaw MU twitch tensions is extremely difficult, because it is affected by the location used to measure the twitch, the background firing rate, muscle coactivation, and regional, intramuscular mechanics. Finally, there have been very few systematic studies of jaw MU reflex behavior. The most recent have concentrated on exteroceptive suppression and suggest that MU inhibition following intra- and perioral stimulation depends on the location of the MU, its background firing rate, the timing of the stimulus, and the task used to drive the unit. Task dependency is a common feature of human jaw MU behavior, reflecting interaction between peripheral sensory information from orofacial and muscle afferents and corticobulbar drive.(ABSTRACT TRUNCATED AT 400 WORDS)

Dynamic jaw delivery on the TomoTherapy H-series platform, entitled TomoEDGE™, is an effective tool to decrease the patient dose along the superior and inferior edges of the treatment target. The aperture of the TomoTherapy jaws, that is, field width (FW), defines the longitudinal dose profile. A consistent FW dose profile is an important quantity for accurate and reproducible dose delivery in TomoTherapy. To date, no evaluation has been made of the accuracy and precision of the dose profiles produced by dynamic jaws. This study aims to provide a long-term evaluation of the dynamic jaw FW dose profiles obtained on TomoTherapy utilizing the TomoTherapy Quality Assurance procedure (TQA). A total of 840 dose profiles were measured during 84 TQA procedures, performed over a 2-yr period. The full width at half maximum (FWHM) and constancy of the FW dose profile measurements were analyzed and compared with the tolerances proposed by AAPM Task Group 148 (TG-148) and those used by the manufacturer. The FWHM evaluation showed that the FWs > 2.0 cm respect the TG-148 tolerance of 1%, while the asymmetric FWs ≤ 2.0 cm were outside the limit in 17.3% of measurements. Constancy results evaluated along the full profiles showed that 95.2% of measurements were within 3% of the baseline for symmetric FWs and 94.8% of measurements were within 4% of the baseline for asymmetric FWs. In conclusion, the analysis confirms the accuracy and precision of TomoEDGE™ technology in jaw positioning. This study has identified the potential to establish an appropriate QA tolerance for the asymmetric FWs used in dynamic jaw movement. Finally, the clinical significance of the observed discrepancies should be studied further to understand the dosimetric effect on patient treatments.

The evolution of the mammalian jaw during the transition from non-mammalian synapsids to crown mammals is a key event in vertebrate history and characterised by the gradual reduction of its individual bones into a single element and the concomitant transformation of the jaw joint and its incorporation into the middle ear complex. This osteological transformation is accompanied by a rearrangement and modification of the jaw adductor musculature, which is thought to have allowed the evolution of a more-efficient masticatory system in comparison to the plesiomorphic synapsid condition. While osteological characters relating to this transition are well documented in the fossil record, the exact arrangement and modifications of the individual adductor muscles during the cynodont-mammaliaform transition have been debated for nearly a century. We review the existing knowledge about the musculoskeletal evolution of the mammalian jaw adductor complex and evaluate previous hypotheses in the light of recently documented fossils that represent new specimens of existing species, which are of central importance to the mammalian origins debate. By employing computed tomography (CT) and digital reconstruction techniques to create three-dimensional models of the jaw adductor musculature in a number of representative non-mammalian cynodonts and mammaliaforms, we provide an updated perspective on mammalian jaw muscle evolution. As an emerging consensus, current evidence suggests that the mammal-like division of the jaw adductor musculature (into deep and superficial components of the m. masseter, the m. temporalis and the m. pterygoideus) was completed in Eucynodontia. The arrangement of the jaw adductor musculature in a mammalian fashion, with the m. pterygoideus group inserting on the dentary was completed in basal Mammaliaformes as suggested by the muscle reconstruction of Morganucodon oehleri. Consequently, transformation of the jaw adductor musculature from the ancestral ('reptilian') to the mammalian condition must have preceded the emergence of Mammalia and the full formation of the mammalian jaw joint. This suggests that the modification of the jaw adductor system played a pivotal role in the functional morphology and biomechanical stability of the jaw joint.

Osteosarcoma (OS) is the most common cancer of bone. Jaw osteosarcoma (JOS) is rare and it differs from other OS in terms of the time of occurrence (two decades later) and better survival. The aim of our work was to develop and characterize specific mouse models of JOS.

No abstract available

Background: Head and neck fibrosarcoma is a rare malignant tumor, accounting for about 1% of all head and neck tumors. It can also occur in the jaw bone, for which surgical resection is the main treatment but the recurrence rate is high and the prognosis is usually poor. Due to the lack of models mimicking the biological characteristics of the tumor, there is little progress in the research of the pathogenesis and treatment of fibrosarcoma. Therefore, there is an urgent need to explore a high-fidelity model that can reflect the biological characteristics of fibrosarcoma for the sake of improving the therapeutic outcome and prognosis, and preventing recurrence. Patient-derived xenografts (PDX) may more accurately reflect the human disease, and is an attractive platform to study disease biology and develop treatments and biomarkers. In this study we describe the establishment of jaw fibrosarcoma PDX models and compare PDX tumors to those of human origin. Methods: Tumor biopsies from a patient with jaw fibrosarcoma were implanted in immunodeficient mice. Primary and PDX tumors were characterized extensively by histology, immunohistochemistry and humanized identification. Based on the finding of our previous preliminary research that plumbagin had an anti-tumor effect against head and neck cancer, we used this model in the present study to evaluate the anti-tumor effect of plumbagin on jaw fibrosarcoma. Results: The established PDX model maintained the histological and immunohistochemical characteristics of the primary tumor. Plumbagin significantly inhibited the tumor growth in the jaw fibrosarcoma PDX model. Conclusion: We successfully established a PDX model of jaw fibrosarcoma and demonstrated that this PDX model preserved the important molecular characteristics of the human primary tumor, thus providing a powerful tool for treatment research and new drug development of jaw fibrosarcoma. In addition, plumbagin was found to have an inhibitory effect on the growth of PDX modeled jaw fibrosarcoma, which provides a preliminary research basis for its clinical application.

To achieve safer patient treatments, serum-free cell culture conditions have to be established for cell therapies. In previous studies, we demonstrated that serum-free culture favored the proliferation of MSCA-1+ osteoprogenitors derived from the jaw periosteum. In this study, the in vitro formation of bone-specific matrix by MSCA-1+ jaw periosteal cells (JPCs, 3 donors) was assessed and compared under serum-free and serum-containing media conditions using the marker-free Raman spectroscopy. Based on a standard fluorescence assay, JPCs from one patient were not able to mineralize under serum-containing culture conditions, whereas the other cells showed similar mineralization levels under both conditions. Raman spectra from mineralizing MSCA-1+ JPCs revealed higher levels of hydroxyapatite formation and higher mineral to matrix ratios under serum-free culture conditions. Higher carbonate to phosphate ratios and higher crystallinity in JPCs cultured under serum-containing conditions indicated immature bone formation. Due to reduced collagen production under serum-free conditions, we obtained significant differences in collagen maturity and proline to hydroxyproline ratios compared to serum-free conditions. We conclude that Raman spectroscopy is a useful tool for the assessment and noninvasive monitoring of in vitro mineralization of osteoprogenitor cells. Further studies should extend this knowledge and improve JPC mineralization by optimizing culture conditions.

Several recent reports have described osteonecrosis of the jaws (ONJ) associated with the use of bisphosphonates. Rheumatologists treating bone diseases with bisphosphonate need, therefore, to be aware of this potential risk and plan the prophylaxis, early diagnosis and prevention of potential consequences. We review the literature on this newly described complication, with particular focus on systemic and local predisposing pathologies, preventive measures suggested before and during therapy with bisphosphonates, and the most frequent clinical presentation of the oral lesions. The expert panel recommendations for the management of care of patients who develop ONJ are summarized.

This review article aimed to introduce a category of jaw lesions associated with impacted tooth. General search engines and specialized databases such as Google Scholar, PubMed, PubMed Central, MedLine Plus, Science Direct, Scopus, and well-recognized textbooks were used to find relevant studies using keywords such as "jaw lesion", "jaw disease", "impacted tooth", and "unerupted tooth". More than 250 articles were found, of which approximately 80 were broadly relevant to the topic. We ultimately included 47 articles that were closely related to the topic of interest. When the relevant data were compiled, the following 10 lesions were identified as having a relationship with impacted tooth: dentigerous cysts, calcifying odontogenic cysts, unicystic (mural) ameloblastomas, ameloblastomas, ameloblastic fibromas, adenomatoid odontogenic tumors, keratocystic odontogenic tumors, calcifying epithelial odontogenic tumors, ameloblastic fibro-odontomas, and odontomas. When clinicians encounter a lesion associated with an impacted tooth, they should first consider these entities in the differential diagnosis. This will help dental practitioners make more accurate diagnoses and develop better treatment plans based on patients' radiographs.

Acquisition of the lower jaw (mandible) was evolutionarily important for jawed vertebrates. In humans, syndromic craniofacial malformations often accompany jaw anomalies. The basic helix-loop-helix transcription factor Hand2, which is conserved among jawed vertebrates, is expressed in the neural crest in the mandibular process but not in the maxillary process of the first branchial arch. Here, we provide evidence that Hand2 is sufficient for upper jaw (maxilla)-to-mandible transformation by regulating the expression of homeobox transcription factors in mice. Altered Hand2 expression in the neural crest transformed the maxillae into mandibles with duplicated Meckel's cartilage, which resulted in an absence of the secondary palate. In Hand2-overexpressing mutants, non-Hox homeobox transcription factors were dysregulated. These results suggest that Hand2 regulates mandibular development through downstream genes of Hand2 and is therefore a major determinant of jaw identity. Hand2 may have influenced the evolutionary acquisition of the mandible and secondary palate.

The surgical treatment of the mandibular and maxillary deformities in patients with hemifacial microsomia requires some form of mandibular lengthening. This is usually either via ramus interpositional bone grafting or end-on bone grafting. In a few cases, ramus lengthening may be completed by a sagittal split. Once the mandible has been reconstructed, the maxillary surgery can be completed. In previous forms of treatment, mandibular bone grafting was completed without regard to function and neuromuscular adaptation and a significant percentage of such procedures completed failed. Egil Harvold and his colleagues developed a method by which changes in form and function are co-ordinated by using a functional appliance resulting in neuromuscular adaptation. After the bone grafting is completed, as the second of six phases of treatment, a specially designed registration bite-block further facilitates neuromuscular adaptation by controlling mandibular movements (function), but in addition it protects the bone graft from excessive forces thereby aiding in osteogenesis (third phase). The theoretical basis, classification of deformities, and phases of treatment developed are presented and the surgery is described in detail. The results of a consecutive group of patients treated by these methods is then presented. While this form of treatment is not the only one possible, it is the only one that has been tested in the laboratory, proven in patient care, and stood the test of time.

Pentoxifylline (PTX) is a methylxanthine derivative that has been implicated in the pathogenesis of peripheral vessel disease and intermittent lameness. The purpose of this study was to investigate the effect of PTX and tocopherol in patients diagnosed with osteoradionecrosis (ORN), bisphosphonate-related osteonecrosis of the jaw (BRONJ), and chronic osteomyelitis using digital panoramic radiographs.

The purpose of this study was to provide a cross-sectional view of all registered clinical trials enrolling patients with osteonecrosis of the jaw (ONJ). The primary aim was to report predictors of trial completion and publication of results.

Clinical application of tissue engineering products requires the exclusion of immune responses after implantation. We used jaw periosteal cells (JPCs) as a suitable stem cell source and analyzed herein the effects of JPCs on dendritic cell maturation after co-culturing of both cell types. Peripheral blood mononuclear cells (PBMCs) were differentiated to dendritic cells (DCs) by the addition of differentiation cocktails for 7 days in co-culture with undifferentiated and osteogenically induced JPCs. The effects of JPCs on DC maturation were analyzed at the beginning (day 7), in the middle (day 14), and at the end (day 21) of the osteogenesis process. We detected significantly lower DC numbers after co-culturing with JPCs that have previously been left untreated or osteogenically differentiated for 7, 14, and 21 days. Using gene expression analyses, significantly lower IL-12p35 and -p40 and pro-inflammatory cytokine (IFN-γ and TNF-α) levels were detected, whereas IL-8 mRNA levels were significantly higher in DCs. Furthermore, osteogenic media conditions enhanced significantly IL-10 gene expression. We concluded that undifferentiated and osteogenically differentiated JPCs had an overall inhibiting influence on dendritic cell maturation. Further studies should clarify the underlaying mechanism in depth.

Bisphosphonate-Related Osteonecrosis of the Jaw (BRONJ) is clinically characterized by the presence of exposed bone in the oral cavity that persists for more than eight weeks. Previous attempts to establish an animal model have not sufficiently considered disease features. Our aim was to establish an inexpensive and replicable animal model that develops BRONJ in a short time.