BACKGROUND: Periodontitis is characterized by alveolar bone resorption, aggravated by osteoblast dysfunction, and associated with intracellular oxidative stress linked to the nuclear factor erythroid 2-related factor 2 (NRF2) level. We evaluated the molecular mechanism of periodontitis onset and development and the role of NRF2 in osteogenic differentiation. METHODS: Primary murine mandibular osteoblasts were extracted and exposed to Porphyromonas gingivalis lipopolysaccharide (Pg-LPS) or other stimuli. Reactive oxygen species (ROS) and 5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolylcarbocyanine iodide (JC-1) staining were used to detect intracellular oxidative stress. Alkaline phosphatase staining and alizarin red S staining were used to detect the osteogenic differentiation of osteoblasts. Immunofluorescence and western blotting were used to determine the changes in the mitogen-activated protein kinase (MAPK) pathway and related molecule activities. Immunofluorescence colocalization and co-immunoprecipitation were performed to examine the nuclear translocation of NRF2 and its interaction with dual-specific phosphatase 1 (DUSP1) in cells. RESULTS: Ligated tissue samples showed higher alveolar bone resorption rate and lower NRF2 level than healthy periodontal tissue samples. Pg-LPS increased intracellular oxidative stress levels and inhibited osteogenic differentiation, whereas changes in NRF2 expression were correlated with changes in the oxidative stress and osteogenesis rate. NRF2 promoted the dephosphorylation of the MAPK pathway by nuclear translocation and the upregulation of DUSP1 expression, thus enhancing the osteogenic differentiation capacity of mandibular osteoblasts. The interaction between NRF2 and DUSP1 was observed. CONCLUSIONS: NRF2 and its nuclear translocation can regulate the osteogenic differentiation of mandibular osteoblasts under Pg-LPS conditions by interacting with DUSP1 in a process linked to the MAPK pathway. These findings form the basis of periodontitis treatment.
Animals ; NF-E2-Related Factor 2/physiology* ; Lipopolysaccharides/pharmacology* ; Osteoblasts/drug effects* ; Mice ; Porphyromonas gingivalis/chemistry* ; Cell Differentiation ; Osteogenesis ; Dual Specificity Phosphatase 1/metabolism* ; Mandible/cytology* ; Reactive Oxygen Species/metabolism* ; Oxidative Stress ; Periodontitis/metabolism* ; Cells, Cultured ; Male ; Cell Nucleus/metabolism*

Tissue interactions play a crucial role in tooth development. Notably, extracellular vesicle-mediated interactions between the mandible and tooth germ are considered essential. Here, we revealed that mandible extracellular vesicles could modulate the proliferation and differentiation of dental mesenchymal cells by regulating the histone demethylase KDM2B. Further investigation showed that mandible derived extracellular vesicles could deliver miR-206 to KDM2B, thereby regulating tooth development. An animal study demonstrated that the miR-206/KDM2B pathway affected tooth morphogenesis and mineralization after eight weeks of subcutaneous transplantation in nude mice. In conclusion, this study suggested that the mandible played a critical role in tooth morphogenesis and mineralization, which could be a potential therapeutic target for abnormal tooth development and an alternative model for tooth regeneration.
Animals ; Extracellular Vesicles/metabolism* ; Jumonji Domain-Containing Histone Demethylases/metabolism* ; Swine ; MicroRNAs/metabolism* ; Mandible ; Mice, Nude ; Odontogenesis/physiology* ; Swine, Miniature ; Mice ; Cell Differentiation ; Cell Proliferation

Chewing-side preference is one of the risk factors for temporomandibular disorders (TMD), and people with chewing-side preference is more prone to have short and displaced condyles, increased articular eminence inclination and glenoid fossa depth. The proportion of TMD patients with chewing-side preference is often higher than that of the normal subjects. Clinical studies have shown a strong correlation between chewing-side preference and TMD symptoms and signs; and animal studies have shown that chewing-side preference can affect the growth, development, damage and repair of the mandible. After long-term unilateral mastication, changes in the stress within the joint cause the imbalance of temporomandibular joint (TMJ) structural reconstruction, the transformation and even destruction of the fiber structure of masticatory muscle, resulting in uncoordinated movement of bilateral muscles. The joint neurogenic diseases caused by the increase of neuropeptide substance P and calcitonin-gene-related-peptide (CGRP) released locally by TMJ may be the mechanism of TMD. This article reviews the research progress of the influence of chewing-side preference on the structure of TMJ, the relationship between chewing-side preference and TMD, and the related mechanisms.
Humans ; Mastication/physiology* ; Temporomandibular Joint/physiology* ; Temporomandibular Joint Disorders/etiology* ; Mandible/physiology*

Biodynamics of mandibular angle fractures has been extensively discussed in the literature in search for the best way to fixate and expedite recovery of trauma patients. Pioneers like Michelet and Champy had the greatest impact on evolving of osteosynthesis in maxillofacial traumatology; they introduced their basic principles frequently used to describe the biomechanics of mandibular fixation. Their concept states when a physiologic load is applied on mandibular teeth a negative tension will be created at superior border and a positive pressure will appear at inferior border. These simple definitions are the basis for the advent of fixation modalities in mandibular angle fracture. This article sought to reassess these principals based on load location via finite elements method.
Biomechanical Phenomena ; Dental Stress Analysis ; Finite Element Analysis ; Fracture Fixation, Internal ; methods ; Humans ; Mandible ; physiopathology ; Mandibular Fractures ; physiopathology ; surgery ; Tooth ; physiology

OBJECTIVEThis work investigated mesenchymal stem cells (MSCs) modified with Runt-related transcription factor 2 (Runx2) therapy for bone regeneration in rabbit mandibular distraction osteogenesis.

METHODSForty-eight New Zealand mature white rabbits were randomly divided into three groups after the rabbit model of mandibular distraction osteogenesis was established: reconstruction plasmid modified with Runx2 (group A), plasmid without Runx2 (group B), and the same dose of saline as control (group C). At the fifth day of distraction phase, MSCs with reconstruction plasmid modified with adv-hRunx2-gfp were injected into the distraction gap of group A. MSCs with reconstruction plasmid modified with adv-gfp was injected into the distraction gap of group B, whereas group C was injected with the same dose of saline. At 8 weeks after injection, all animals were sacrificed, and the distracted mandibles were harvested. The general imaging histological observation and three-point bending test were used for evaluation.

RESULTSCT plain scan and histological analysis confirmed that the amount of new bone forming in the distraction gap of group A was significantly higher than those in groups B and C. Dual-energy X ray and three-point bending test results also showed that the bone mineral density, bone mineral content, and maximum load of the distraction gap of group A were significantly higher than those of groups B and C (P<0.01).

CONCLUSIONRunx2-ex vivo gene therapy based on MSCs can effectively promote the bone regeneration in rabbit mandibular distraction osteogenesis and shorten the stationary phase. Therefore, reconstruction of craniofacial fracture would be a valuable strategy

Absorptiometry, Photon ; Animals ; Bone Density ; Bone Regeneration ; physiology ; Core Binding Factor Alpha 1 Subunit ; genetics ; pharmacology ; Genetic Therapy ; Mandible ; physiology ; surgery ; Mesenchymal Stem Cell Transplantation ; methods ; Mesenchymal Stromal Cells ; Osteogenesis ; genetics ; Osteogenesis, Distraction ; methods ; Plasmids ; Rabbits ; Random Allocation ; Transcription Factors ; genetics ; physiology ; Treatment Outcome

BACKGROUND: Prenatal tongue development may affect oral-craniofacial structures, but this muscular organ has rarely been investigated. METHODS: In order to document the physiology of prenatal tongue growth, we histologically examined the facial and cranial base structures of 56 embryos and 106 fetuses. RESULTS: In Streeter's stages 13-14 (fertilization age [FA], 28 to 32 days), the tongue protruded into the stomodeal cavity from the retrohyoid space to the cartilaginous mesenchyme of the primitive cranial base, and in Streeter's stage 15 (FA, 33 to 36 days), the tongue rapidly swelled and compressed the cranial base to initiate spheno-occipital synchondrosis and continued to swell laterally to occupy most of the stomodeal cavity in Streeter's stage 16-17 (FA, 37 to 43 days). In Streeter's stage 18-20 (FA, 44 to 51 days), the tongue was vertically positioned and filled the posterior nasopharyngeal space. As the growth of the mandible and maxilla advanced, the tongue was pulled down and protruded anteriorly to form the linguomandibular complex. Angulation between the anterior cranial base (ACB) and the posterior cranial base (PCB) was formed by the emerging tongue at FA 4 weeks and became constant at approximately 124degrees-126degrees from FA 6 weeks until birth, which was consistent with angulations measured on adult cephalograms. CONCLUSIONS: The early clockwise growth of the ACB to the maxillary plane became harmonious with the counter-clockwise growth of the PCB to the tongue axis during the early prenatal period. These observations suggest that human embryonic tongue growth affects ACB and PCB angulation, stimulates maxillary growth, and induces mandibular movement to achieve the essential functions of oral and maxillofacial structures.
Adult ; Axis, Cervical Vertebra ; Embryonic Structures* ; Fetus* ; Humans ; Mandible ; Maxilla ; Mesoderm ; Parturition ; Physiology ; Skull Base ; Tongue*

OBJECTIVETo explore the effect of recombinant human parathyroid hormone 1-34 [rhPTH(1-34)] on bone regeneration rabbit mandible during distraction osteogenesis (DO).

METHODS40 Japanese white rabbit (weight 2.0-2.5 kg) were randomly divided into control group and groups. The experimental groups were divided inito 12.5, 25 and 50 µg/kg group according to the dosage of rhPTH (1-34) in each group. Each group involved 10 rabbits, and unilateral DO models were established at the right mandible of the rabbits. From the first day of distraction to the day of execution, the rabbits in the experimental groups were injected subcutaneously rhPTH (1-34) of the corresponding dose respectively, and the rabbits in the control group were injected subcutaneously 2% heat inactivated rabbit serum 1 ml respectively.. Five rabbits in each group were executed respectively at 1 week and 3 weeks after completion of distraction, and the specimens of DO were harvested. The gross observation, X-ray examination, and histological study were performed.

RESULTSGross appearance: At the first week of consolidation, the dense and opaque white tissue was seen in the distraction gap of the 50 µg/kg group, and the white translucent tissue was seen in the distraction gaps of the rest groups. At the third week of consolidation, the greyish white tissue was seen in the distraction gap of the control group, while the cartilage-like tissue was seen in the buccal side of the distraction gap of the 12.5 µg/kg group, the color of new-formed tissues was close to that of normal bone tissue in the lingual side. The buccal tissue at the edge of the distraction gap of the 25 µg/kg group fitted together with the primary bone tissue in its two sides. It was difficult to distinguish the boundaries between the distraction gap and the bone tissues in its two sides in the 50 µg/kg group. X-ray findings: At the first week of consolidation, a sparse opaque image was seen in the distraction gap of the 50 µg/kg group, and a low-density image was seen in the distraction gap of the rest groups. At the third week of consolidation, a sparse bone image was seen in the control group, and the edge of the bone was not continuous. With the increase of the dose in the experimental groups, the image of the distraction gap became more and more opaque, and the image of the distraction gap in the 50 µg/kg group was close to that of the normal bone tissue. HISTOLOGICAL FINDINGS: At the first week of consolidation, few osteoblasts were present at the edge of the distraction gap of the control group. A large number of bone cells and bone trabecular were present in the distraction gap of the 12.5 µg/kg group, the network of the bone trabecula was present in the 25 µg/kg group, and a few new bones were found in the 50 µg/kg group. At the third week of consolidation, the network of the trabecular bone was present in the distraction gap of the control group, while the network of the bone trabecula was present in the 12.5 µg/kg group, a lot of bone-like tissues in the 25 µg/kg group, and near-mature bone in the 50 µg/kg group.

CONCLUSIONSrhPTH(1-34) can promote the formation of new bone in the distracted gap during mandibular DO in rabbits.

Animals ; Bone Density ; Bone Regeneration ; drug effects ; physiology ; Humans ; Mandible ; drug effects ; surgery ; Osteogenesis, Distraction ; methods ; Parathyroid Hormone ; pharmacology ; Rabbits ; Random Allocation ; Recombinant Proteins ; pharmacology

OBJECTIVETo investigate the effect of the biofeedback in regulating the myoelectric activities of the masseter muscles.

METHODSTwenty orthodontic patients aged from 10 to 14 years with Angle Class II malocclusion, retrusive mandible, and an ANB angle > 6° were enrolled in this study. The muscular activities of the anterior temporal muscle and the masseter muscle were evaluated before, during, and after biofeedback treatment by assessing the average integrated electromyogram and temporal/masseter (T/M) ratio in the clenching status.

RESULTSThe patients' myoelectric activities of the anterior temporal muscle was significantly increased after biofeedback treatment (P<0.05). The patients' T/M ratio in the clenching status was increased after the treatment (1.76 ± 1.46 before treatment, 4.71 ± 4.03 immediately after treatment, and 2.57 ± 2.07 at 1 day after treatment; t=4.86, P<0.05).

CONCLUSIONBiofeedback treatment can regulate the activities of the anterior temporal and masseter muscles and increase the T/M ratio in the clenching status.

Adolescent ; Biofeedback, Psychology ; Child ; Electromyography ; Humans ; Malocclusion, Angle Class II ; Mandible ; Masseter Muscle ; physiology ; Temporal Muscle ; physiology

We investigated the compensatory trends of mesiodistal angulation of first molars in malocclusion cases. We compared differences in the angulation of first molars in different developmental stages, malocclusion classifications and skeletal patterns. The medical records and lateral cephalogrammes of 1403 malocclusion cases taken before treatment were measured to evaluate compensation of molar angulation in relation to the skeletal jaw. The cases were stratified by age, Angle classification and skeletal patterns. Differences in the mesiodistal angulation of the first molars were compared among the stratifications. We observed three main phenomena. First, angulation of the upper first molar varied significantly with age and tipped most distally in cases aged <12 years and least distally in cases aged >16 years. The lower first molar did not show such differences. Second, in Angle Class II or skeletal Class II cases, the upper first molar was the most distally tipped, the lower first molar was the most mesially tipped, and opposite angulation compensation was observed in Class III cases. Third, in high-angle cases, the upper and lower first molars were the most distally tipped, and opposite angulation compensation was observed in low-angle cases. These data suggest that the angulation of the molars compensated for various growth patterns and malocclusion types. Hence, awareness of molar angulation compensation would help to adjust occlusal relationships, control anchorage and increase the chances of long-term stability.
Adolescent ; Adult ; Age Factors ; Anatomic Landmarks ; pathology ; Cephalometry ; methods ; Child ; Cohort Studies ; Dentition, Mixed ; Female ; Humans ; Male ; Malocclusion ; classification ; pathology ; Malocclusion, Angle Class I ; pathology ; Malocclusion, Angle Class II ; pathology ; Malocclusion, Angle Class III ; pathology ; Mandible ; pathology ; Maxilla ; pathology ; Maxillofacial Development ; physiology ; Middle Aged ; Molar ; pathology ; Palate ; pathology ; Retrospective Studies ; Young Adult

The purpose of this study was to evaluate whether the cranial and circumaxillary sutures react differently to maxillary expansion (ME) and alternate maxillary expansions and constrictions (Alt-MEC) in a rat model. Twenty-two male Sprague-Dawley rats (6 weeks old) were used and divided into three groups. In ME group (n=9), an expander was activated for 5 days. In Alt-MEC group (9 animals), an alternate expansion and constriction protocol (5-day expansion and 5-day constriction for one cycle) was conducted for 2.5 cycles (25 days total). The control group comprised 4 animals with no appliances used, each of two sacrificed on day 5 and day 25 respectively. Midpalatal suture expansion or constriction levels were assessed qualitatively and quantitatively by bite-wing X-rays and cast models. Distances between two central incisors and two maxillary first molars were measured on cast models after each activation. Circumaxillary sutures (midpalatal, maxillopalatine, premaxillary, zygomaticotemporal and frontonasal suture) in each group were characterized histologically. Results showed that midpalatal suture was widened and restored after each expansion and constriction. At the end of activation, the widths between both central incisors and first molars in Alt-MEC group were significantly larger than those in ME group (P<0.05). Histologically, all five circumaxillary sutures studied were widened in multiple zones in Alt-MEC group. However, only midpalatal suture was expanded with cellular fibrous tissue filling in ME group. Significant osteoclast hyperplasia was observed in all circumaxillary sutures after alternate expansions and constrictions, but osteoclast count increase was only observed in midpalatal suture in ME group. These results suggested that cranial and circumaxillary sutures were actively reconstructed after Alt-MEC, while only midpalatal suture had active reaction after ME.
Animals ; Male ; Mandible ; anatomy & histology ; physiology ; Masticatory Muscles ; anatomy & histology ; physiology ; Maxilla ; anatomy & histology ; physiology ; Range of Motion, Articular ; physiology ; Rats ; Rats, Sprague-Dawley