Association between an Increased Serum CCL5 Level and Pathophysiology of Degenerative Joint Disease in the Temporomandibular Joint in Females.

Degenerative joint disease of the temporomandibular joints (DJD-TMJ) clinically manifests with symptoms such as orofacial pain, joint sounds and limited jaw movements. Our research group previously reported the functional necessity of a chemokine-chemokine receptor axis of CCL5-CCR5 in osteoclasts. Accumulated studies reported that this axis was involved in the pathogenesis of bone and joint destructive diseases, suggesting CCL5 as a potent biomarker. This study investigated whether or not the serum level of CCL5 can be a biomarker of DJD-TMJ and concomitantly analyzed changes in the serum and urine levels of bone markers to see whether or not changes in the rate of bone metabolism were predisposing. We enrolled 17 female subjects with diagnosed DJD-TMJ and sexually and age-matched 17 controls. The serum CCL5 level in DJD-TMJ subjects was significantly higher than that in the control subjects. Multivariate analyses indicated an association between an augmented CCL5 level and the rate of bone metabolism, especially in relatively young DJD-TMJ subjects without other systemic symptoms. A principal component analysis of serum markers and our pharmacological experiment using a postmenopausal model of ovariectomized rats suggested that an augmented serum CCL5 level specifically reflected DJD-TMJ and that covert changes in the rate of bone metabolism predisposed individuals to DJD-TMJ.

Whole-exome sequencing in a Japanese pedigree implicates a rare non-synonymous single-nucleotide variant in BEST3 as a candidate for mandibular prognathism.

Mandibular prognathism is a phenotype of facial deformity seen in populations around the world, but with higher incidence among East Asian populations. Five genome-wide nonparametric linkage analyses and a genome-wide association study to identify susceptibility loci of the phenotype have shown inconsistent results. To explore variants related to mandibular prognathism, we undertook whole-exome sequencing in a Japanese pedigree. The pedigree was ascertained as mandibular prognathism. The pedigree comprised 15 individuals from 4 generations. Four affected individuals across 2 generations and 5 unaffected individuals were chosen for whole-exome sequencing. Five non-synonymous single-nucleotide variants (SNVs) of UBASH3B, OR6M1, OR8D4, OR8B4, and BEST3 genes were detected in all 4 affected individuals, but in none of the 5 unaffected individuals. A non-synonymous SNV of the BEST3 gene, Chr12(GRCh37):g.70048878G>T, NM_032735.2:c.1816C>A, p.(L606I), was identified as rare missense variant. BEST3 is located on chromosome 12q15 and encodes bestrophin 3 from the bestrophin family of anion channels. The 4 other non-synonymous SNVs of UBASH3B, OR6M1, OR8D4, and OR8B4 were not considered plausible candidates for mandibular prognathism. Our whole-exome sequencing implicates a rare non-synonymous SNV of BEST3 as a candidate for mandibular prognathism in the Japanese pedigree.

Clinical Investigation of Congenital Factor Affecting Craniofacial Morphology of Unilateral Cleft Lip and Palate in Japanese Patients

Objective: To evaluate the craniofacial morphology of Japanese patients with unilateral cleft lip and palate and to evaluate the multiple congenital factors that affects craniofacial morphology in unilateral cleft lip and palate patients. Material and Methods: Lateral cephalograms of 140 subjects with unilateral cleft lip and palate were taken before any orthodontic treatment and alveolar bone graft. Subjects mean age was 6.85 ±1.56 years. Primary surgeries performed by surgeons from Hokkaido University Hospital. The craniofacial morphology of the 140 subjects was assessed by angular and linear cephalometric measurements. Gender, side of cleft, complete/incomplete type of cleft, presence/absence of lateral incisor in the affected side, family history of cleft and family history of skeletal Class III was chosen as congenital factors. To compare the assessments using congenital factors affecting craniofacial morphology in the unilateral cleft lip and palate subjects, angular and linear cephalometric measured values from each individual subject (control group) were converted into Z scores in relation to the means and standard deviation of the two parameters. Results: Twelve out of 13 craniofacial morphology outcomes were insignificant in 5 out of 6 dependent variables. Only 1 dependent variable showed 3/13 significant differences. Conclusion: Current study revealed the evidence that there were almost no significant differences in the craniofacial morphology outcome among various congenital factors. This will provide base line information and help determine the effectiveness of such factors.

Treatment Outcome Based on GOSLON Score of Multiple Factors in Unilateral Cleft Lip and Palate Children of Four Different Ethnic

Objective: To evaluate and compare the effect of each congenital and postnatal treatment factors in treatment outcome based on dental arch relationship (DAR) of four different populations at a time using GOSLON yardstick. Material and Methods: 432 unilateral cleft lip and palate subjects (Japanese, Malay ethnic group, Bangladeshi and Pakistani populations) age 5 to 12 years were taken before orthodontic treatment and alveolar bone grafting. The DAR was assessed by GOSLON Yardstick. Independent t-test was performed to compare the GOSLON score for each factors. A multiple comparison (Anova) was also conducted between the GOSLON score of four different populations. The significance level was set at p<0.05. Results: Statistically no significant different was found among the congenital factors. However, the family history of Class III malocclusion showed most likely to associate with, though there was no significant difference (p=0.069). Significant difference revealed between two techniques of cheiloplasty in both Malay ethnic group and Pakistani population (p=0.038 and p=0.000, respectively). Gender and Techniques of palatoplasty also showed significant difference in Pakistani population (p=0.026 and p=0.000, respectively). Japanese and Bangladeshi population showed no significant differences. Also no significant differences found between the GOSLON score and different countries. Conclusion: The treatment outcome based on DAR significantly varies in individual population [Malay ethnic group (cheiloplasty); Pakistan (gender, cheiloplasty and palatoplasty)].

Maxillofacial morphological factors related to acceleration of maxillary growth attributed to facial mask treatment: a structural superimposition study.

BACKGROUND: Anatomical textbooks mention that the contact between the pterygoid process and the palatine's pyramidal process is not a "suture" but "conjugation.".The aim was to evaluate the maxillofacial morphological factor responding most to the orthopedic force of facial mask treatment, using the structural superimposition analysis. METHODS: Thirty-one girls with Angle Class III malocclusion treated using a facial mask (FM group) and 11 girls with pseudo-Class III malocclusion (pseudo-III group) were examined. Lateral cephalograms at pre- and posttreatment were analyzed to evaluate maxillofacial changes. Cephalometric structural superimposition analysis originating with Björk and Skieller was also performed. RESULTS: In the FM group, a multiple linear regression model showed that maxillary sutural growth was significantly associated with counter-clockwise rotation of the maxilla and treatment changes in the anteroposterior distance from the pterygomaxillary fissure to the maxillary anterior alveolus, not changes in the distance from the nasion to the maxillary anterior alveolus. CONCLUSIONS: Structural superimposition analysis showed that counter-clockwise rotation of the maxilla and changes in the distance from the pterygomaxillary fissure to the maxillary anterior alveolus responded most to the orthopedic force of facial mask treatment. The analysis implicated that the pterygoid fissure-palatine's pyramidal process conjugation responds most to facial mask treatment among maxillofacial sutures and conjugation, and that the difference in the response induces maxillary counter-clockwise rotation.

Osseous changes of the mandibular condyle affect backward-rotation of the mandibular ramus in Angle Class II orthodontic patients with idiopathic condylar resorption of the temporomandibular joint.

Objective: To evaluate whether osseous changes of the temporomandibular joint (TMJ) condyle affect backward rotation of the mandibular ramus in Angle Class II orthodontic patients with idiopathic condylar resorption (ICR). Methods: Twenty Japanese women with Class II malocclusion with ICR (ICR group) and 24 women with Class II malocclusion without ICR (non-ICR group) were examined. Pre-treatment panoramic radiographs were used to measure condylar ratios. Pre-treatment lateral cephalograms were used to evaluate maxillofacial morphology. Results: The ICR group had a significantly smaller condylar ratio, greater backward rotation of the ramus, less labially inclined upper incisors, and a steeper occlusal plane. The increased backward rotation of the ramus in the ICR group was significantly associated with a smaller condylar ratio. Conclusion: Angle Class II patients with ICR had shorter condylar height attributable to osseous changes of the TMJ condyle, and the shorter condylar height may affect subsequent backward rotation of the ramus.

PLXNA2 identified as a candidate gene by genome-wide association analysis for mandibular prognathism in human chondrocytes.

In a previous genome-wide association study, plexin A2 (PLXNA2) was suggested as one of the candidate genes for mandibular prognathism. PLXNA2 encodes plexin A2, a member of the plexin-A family of semaphorin co-receptors. Semaphorin 3A (sema3A) exerts an osteoprotective effect. However, to the best of our knowledge, there have been no previous studies examining the role of sema3A or plexin A2 on human chondrocytes. The objectives of the present study were to examine the function of sema3A and its receptor, plexin A2, in human chondrocytes. Normal human chondrocytes were cultured in media with either a high (100 ng/ml) or a low (1 ng/ml) concentration of sema3A, or without sema3A as a control. Cells and extracellular matrices were assayed for concentrations of protein and parathyroid hormone-related peptide receptor 1 (PTH-R1) using a bicinchoninic acid assay and an enzyme immunoassay, respectively. At culture day 7, the high and low concentrations of exogenous sema3A significantly increased the protein content compared with the control (P=0.0008 and 0.00002, respectively). At culture day 14, a high concentration of exogenous sema3A significantly increased the protein content and decreased the concentration of PTH-R1 compared with the control (P=0.002). The present study revealed novel results that exogenous sema3A suppresses the expression of PTH-R1 in human proliferative chondrocytes and suggested that sema3A may affect human chondrocytes via its receptor, plexin A2.

Genome-wide association study for mandibular prognathism using microsatellite and pooled DNA method.

INTRODUCTION: The purpose of this study was to extend an association study from chromosome 1 to the whole genome (genome-wide association study) to find susceptibility loci of mandibular prognathism. METHODS: Two hundred forty patients diagnosed with mandibular prognathism and 360 healthy controls of Japanese descent were recruited. The typing of microsatellites covering the whole genome was conducted using a pooled DNA method. Upon completion of the first and second screenings with pooled DNA, the positive microsatellite markers from both the first and second typings were retyped using individual-subject DNA samples to confirm the significance of allele frequency. RESULTS: Six microsatellites (D1S0411i, D1S1358i, D3S0810i, D6S0827i, D7S0133i, and D15S0154i) showed differences between allele frequencies of the subjects and controls at P <0.001. D1S0411i, D1S1358i, D3S0810i, D6S0827i, D7S0133i, and D15S0154i were located on chromosomes 1p22.3, 1q32.2, 3q23, 6q23.2, 7q11.22, and 15q22.22, respectively. SSX2IP, PLXNA2, RASA2, TCF21, CALN1, and RORA were suggested as candidate genes. CONCLUSIONS: The genome-wide association study using microsatellites suggested that 6 loci (1p22.3, 1q32.2, 3q23, 6q23.2, 7q11.22, and 15q22.22) were susceptibility regions of mandibular prognathism. The locus 1p22.3 was supported by a previous linkage analysis, and the other 5 were novel loci.

Microsatellite genome-wide association study for mandibular prognathism.

INTRODUCTION: Attempts have been made to identify susceptibility genes of mandibular prognathism by genome-wide linkage studies, but the results of susceptibility loci are inconsistent. There has been no genome-wide association study of mandibular prognathism. Our objective was to perform a genome-wide association study using 23,465 microsatellite markers to detect mandibular prognathism susceptibility regions. METHODS: The study was based on the pooled DNA method, including 2 steps of screening on the whole genome and subsequent individual genotyping, with 240 experimental subjects and 360 control subjects from the Japanese population. RESULTS: Two suggestive associations on chromosomes 1q32.2 (D1S1358i: P = 4.22 × 10(-4)) and 1p22.3 (D1S0411i: P = 6.66 × 10(-4)) were shown, and PLXNA2 and SSX2IP were suggested to be candidate genes; 1p22.3 flanked the region indicated by previous linkage analysis. CONCLUSIONS: The results of the genome-wide association study showed that 2 loci (1q32.2 and 1p22.3) are likely to be susceptibility regions of mandibular prognathism: 1p32.2 is a novel locus, and identification of 1p22.3 supports the results of previous linkage analysis.

Quantitative evaluation of myofibroblast apoptosis during wound healing in rat palate after post-operative administration of basic fibroblast growth factor (bFGF).

OBJECTIVE: Excessive wound contraction apparently inhibits maxillary growth; thus, myofibroblast apoptosis needs to be accelerated in mucoperiosteal denudation after palatoplasty. The aim of this study was to evaluate myofibroblast apoptosis during wound healing in mucoperiosteal denudation of rat palates immediately after post-operative administration of basic fibroblast growth factor (bFGF). MATERIALS AND METHODS: A total of 100 male Wistar rats aged 20 days were divided into control, scar, sham and bFGF groups (n = 25 each). In the scar, sham and bFGF groups, mucoperiosteum was removed from the palate and fibrin glue was applied to the exposed bone surface immediately after surgery. In the bFGF group, 10 µL of 2 µg/µL bFGF solution was injected into the operated area beneath the fibrin glue. At 2, 5, 7, 14 and 28 days post-operatively, myofibroblast apoptosis during the wound healing process was investigated by double immunofluorescence staining. The apoptotic area of myofibroblasts was measured using image software. RESULTS: In the bFGF group, at 2 days, apoptosis of myofibroblasts in the lamina propria and submucosa was marked, as compared with the other three groups and apoptosis of myofibroblasts was scarcely seen at 5 days. At 5 and 7 days, the apoptotic area of myofibroblasts in the bFGF group was statistically significantly smaller when compared to the scar and sham groups. CONCLUSION: The results confirmed that bFGF injection immediately after surgery accelerated apoptosis of myofibroblasts in mucoperiosteal denudation of rats. This may reduce maxillary growth retardation due to excessive wound contraction.

Oxygen saturation and electromyographic changes in masseter muscle during experimental chewing of gum with harder texture.

OBJECTIVE: The purpose of this study was to clarify the relationship between changes in masseter muscle oxygenation measured by near-infrared spectroscopy (NIRS) and changes in the electromyographic (EMG) power spectrum during experimental chewing of gum with harder texture, to improve the understanding of the use of NIRS in assessing masseter muscle fatigue. MATERIAL AND METHODS: Ten female volunteers with normal occlusion were examined. Mean age (standard deviation) was 28.4 (3.8) years. Mean fracture stress of gum was 12.5 × 10(4) N/m(2). Subjects were instructed to chew gum for 60 s (75 strokes) on the voluntary chewing side at a pace of 1.25 strokes/s. Simultaneous recordings of NIRS and EMG signals from masseter muscle were performed during gum chewing. RESULTS: Oxygen saturation levels decreased from the start of chewing, then stabilized with a break point between the two phases. The normalized EMG amplitude increased and the mean frequency of the EMG power spectrum decreased during gum chewing. The timing of break point appearance was related to the timing of a significant decrease in median frequency, but no clear relationships were found between break point appearance and increased EMG amplitude. CONCLUSIONS: These results suggest that the break point of the oxygen saturation curve, as obtained from NIRS measurements, could be used as an indicator of masseter muscle fatigue as assessed by a shift in the EMG power spectrum to lower frequencies.

Congenital and postnatal factors inducing malocclusions in Japanese unilateral cleft lip and palate patients-determination using logistic regression analysis.

Objective : To assess the congenital and postnatal factors that affect degree of malocclusion in patients with unilateral cleft lip and palate using multivariate statistical analysis. Design : Retrospective study. Patients : All information on 135 subjects with unilateral cleft lip and palate was obtained from an oral examination and radiograph at the initial examination at an orthodontic clinic and from surgical records. Plaster models were taken before orthodontic treatment. The ages of the subjects ranged from 5 to 8 years with a mean age of 6.9 years. All primary surgeries for the patients were performed at a university hospital. Main Outcome Measures : The GOSLON Yardstick was used to assess the dental arch relationships (degree of malocclusion) in patients. Family history of Class III, degree of cleft, and congenitally missing upper lateral incisor on the cleft side were chosen as congenital factors inducing malocclusion. Presurgical orthopedic treatment, cheiloplasty, and palatoplasty were chosen as postnatal factors. Associations between various factors and dental arch relationships were assessed using logistic regression analysis. Results : According to adjusted odds ratios, family history of Class III is associated with a significantly worse dental arch relationship. Palatoplasty using push-back alone correlated to a dental arch relationship that was significantly worse than palatoplasty using push-back with a buccal flap. Conclusions : Multivariate analysis shows evidence that a positive family history of Class III and palatoplasty using push-back alone are associated with worse malocclusion of unilateral cleft lip and palate patients.

Postnatal treatment factors affecting craniofacial morphology of unilateral cleft lip and palate (UCLP) patients in a Japanese population.

We have evaluated the craniofacial morphology of Japanese patients with unilateral cleft lip and palate (UCLP) and assessed the various postnatal factors that affect it. Lateral cephalograms of 140 subjects (mean (SD) aged 7 (2) years) with UCLP were taken before orthodontic treatment. Surgeons from Hokkaido University Hospital had done the primary operations. The craniofacial morphology was assessed by angular and linear cephalometric measurements. Cheiloplasty, palatoplasty, and preoperative orthopaedic treatment were chosen as postnatal factors. To compare the assessments of the postnatal factors, we made angular and linear cephalometric measurements for each subject and converted them into Z scores in relation to the mean (SD) of the two variables. Subjects treated by the modified Millard cheiloplasty had larger sella-nasion-point A (SNA) and nasion-point A-pogonion (NA-POG) measurements than subjects treated by the modified Millard with a vomer flap cheiloplasty. Two-stage palatoplasty showed consistently better craniofacial morphology than the other palatoplasty. Subjects who had preoperative orthopaedic treatment with a Hotz plate had significantly larger upper incisor/sella-nasion (U1-SN) measurements than who had no preoperative orthopaedic treatment or an active plate. We conclude that in subjects treated by a modified Millard type of cheiloplasty, a two-stage palatoplasty, and a Hotz plate there were fewer adverse effects on craniofacial morphology.

Three-dimensional craniomaxillary characteristics of the mouse with spontaneous malocclusion using micro-computed tomography.

The aim of this study was to clarify the morphological characteristics of craniomaxillary deviations in BALB/c-bm/bm mice with a spontaneous malocclusion (incisal transverse crossbite) using three-dimensional (3D) morphological measurements. Sixty female mice aged 13 and 25 weeks were divided into the following groups: control (BALB/c-+/+ mice, n = 20), norm (BALB/c-bm/bm mice with a normal occlusion, n = 20), and mal (BALB/c-bm/bm mice with a malocclusion, n = 20). Various points in the skull were selected and the distances between two points were measured using 3D micro-computed tomography (CT) images. Statistically significant differences in measurement values among the three groups were evaluated by one-way analysis of variance with a probability level of P < 0.05 considered statistically significant. At both ages, the lengths of almost all measurements in the norm and mal groups were significantly shorter than those in the control group. Comparison between the shifted and non-shifted sides in the mal group showed that significant lateral deviation at the maxilla and nasal bone had occurred. Using 3D micro-CT images, the results of this study quantitatively showed that the craniomaxillary complex of BALB/c-bm/bm mice was significantly smaller than that of BALB/c-+/+ mice and that BALB/c-bm/bm mice have a spontaneous transverse crossbite due to lateral deviation of the maxilla and nasal bone.

Relationship between degree of malocclusion and occlusal interference in mice that spontaneously develop anterior transverse crossbite.

INTRODUCTION: Mice with brachymorphism (bm) have defective chondrogenesis, including abnormal growth of the spheno-occipital synchondrosis. Malocclusion (anterior transverse crossbite) sometimes spontaneously occurs in inbred BALB/c-bm/bm mice, before the mandibular incisors erupt and make contact with the maxillary incisors. The aim of this study was to determine whether functional lateral loads to incisors promote anterior transverse crossbites in BALB/c-bm/bm mice. METHODS: BALB/c-bm/bm mice with normal occlusion (normal group), BALB/c-bm/bm mice with malocclusion in which the incisors were not cut (mal group), and BALB/c-bm/bm mice in which the incisors had been cut to eliminate the functional lateral load during continued growth (mal-cut group) were used. We examined the amounts of shift of the maxillary and mandibular incisors in each group using radiographic images. RESULTS: The amount of shift of the maxillary incisors in the mal group was significantly greater than that in normal group. The total amount of shift from the maxilla to the mandible in the mal group was significantly greater than in the normal and mal-cut groups. CONCLUSIONS: The results suggest that a continuous functional lateral load to the incisors is strongly related to promoting and worsening anterior transverse crossbite in BALB/c-bm/bm mice.

Interleukin-1beta levels, pain intensity, and tooth movement using two different magnitudes of continuous orthodontic force.

This study aimed to determine the optimum orthodontic force from a broader perspective. Interleukin (IL)-1ß levels in human gingival crevicular fluid (GCF), pain intensity, and the amount of tooth movement were measured during canine retraction using different magnitudes of continuous orthodontic force. Sixteen subjects (two males and 14 females), aged 18-24 years, diagnosed with Class I bimaxillary protrusion and treated with first premolar extractions participated in this study. The upper canines were retracted with continuous forces of 50 or 150 g using nickel-titanium coil springs on segmented archwires. One of the lower canines was used as a control. GCF was collected from the distal site of each tooth at specific time points. IL-1ß concentrations, pain intensity, using the visual analogue scale (VAS), and the amount of tooth movement were evaluated. One-way analysis of variance, Friedman, and paired t-tests were used for comparisons of IL-1ß in GCF, the plaque and gingival indices, and the efficiency of tooth movement on pain perception, respectively. IL-1ß concentration in the 150 g group showed the highest level at 24 hours and 2 months with significant differences compared with the control group (P < 0.05). The mean VAS score of pain intensity from the 150 g force was significantly greater than from the 50 g force at 24 hours (P < 0.01). However, no significant difference in the amount of tooth movement was found between these two different magnitudes of continuous force at 2 months. A 50 g force could effectively induce tooth movement similar to 150 g with less pain and less inflammation.

Monocortical mandibular bone grafting for reconstruction of alveolar cleft.

OBJECTIVE: To assess and develop a monocortical mandibular bone grafting procedure for reconstruction of alveolar cleft. DESIGN: Prospective study. SETTING: Hokkaido University Hospital. PATIENTS: Forty-two consecutive Japanese patients who had been treated for a total of 48 clefts according to a strict clinical protocol. Mean age at bone grafting was 6 years 11 months. INTERVENTIONS: Bone grafting was performed by harvesting lateral cortical bone plates from the symphysis and/or body and then placing them on the labial and palatal openings of the alveolar process defect. No particulate bone grafts were packed into the bony cavity. Mean follow-up after bone grafting was 37 months. MAIN OUTCOME MEASURES: Status of the grafted area and eruption of cleft-adjacent teeth were assessed prospectively using computed tomography and periapical radiography. RESULTS: At 6 months postoperatively, computed tomography showed sufficient bone bridge formation at the cleft site in 85.4% of clefts. Periapical radiography showed ≥75% of the root surfaces of cleft-adjacent teeth were covered with spanning bone in 83.3% of clefts. In 92.6% of clefts in which the cleft-adjacent canine was uncovered with bone during follow-up, the canines erupted spontaneously. CONCLUSIONS: Monocortical mandibular bone grafting appears extremely effective for sufficient bone bridge formation and facilitation of cleft-adjacent teeth eruption. The procedure is advantageous in that the quantity of bone required per unit volume of cleft defect is relatively reduced, and larger clefts can thus be treated.

Orthodontic treatment of cleft lip and alveolus using secondary autogenous cancellous bone grafting: a case report.

AIM: This paper concerns orthodontic alignment of the maxillary lateral incisor on the cleft side of a lip and alveolar cleft patient after a secondary autogenous cancellous bone graft at the late stage of mixed dentition. SUBJECT AND TREATMENT: The patient was a Japanese girl 9 years 7 months of age who presented at the authors' clinic with a repaired lip and alveolar cleft and an incisor crossbite. At 12 years of age, a secondary bone graft of the alveolar ridge was performed using bone harvested from the iliac crest. At 14 years 7 months of age, a conventional fixed appliance was placed. RESULTS: The lateral incisor on the cleft side was brought to the line of occlusion by orthodontic alignment. A Class I molar relationship on both sides and a satisfactory facial profile were achieved. After a 2-year retention period, the occlusion and esthetics were maintained. Five years after grafting, however, a satisfactory bone level was not achieved due to positioning of the root of the lateral incisor, which was not completely upright in the bone graft area due to root tipping.

Growth and development of the cranial base in mice that spontaneously develop anterior transverse crossbite.

INTRODUCTION: Homozygous brachymorphic (bm/bm) mice are characterized by disproportionately short stature. Anterior transverse crossbite sometimes develops spontaneously in inbred BALB/c-bm/bm mice that produce undersulfated glycosaminoglycans. The reason for inferior growth of the craniofacial structures of BALB/c-bm/bm mice has not been clarified. We focused on the spheno-occipital synchondrosis (SOS)-the growth site of the cranium-and investigated the growth pattern in the SOS of the BALB/c-bm/bm mice. METHODS: The BALB/c-+/+ mice and BALB/c-bm/bm mice without malocclusion were used. Sagittal sections of the cranial bases were stained with hematoxylin and eosin, observed histologically, and used to measure the anteroposterior length and the percentage of active bone volume around the SOS. RESULTS: In the histologic study, compared with the cartilage in the BALB/c mice, a bipolar column was not seen in the cartilage of the SOS in the BALB/c-bm/bm mice. The histomorphometric study showed that the anteroposterior length of the posterior cranial base was significantly shorter and the percentage of active bone volume was significantly smaller in the BALB/c-bm/bm mice than in the BALB/c mice. CONCLUSIONS: The results suggested that normal endochondral growth is disturbed in the synchondrosis of the posterior base of the skull in BALB/c-bm/bm mice.

Elevated levels of beta-endorphin in temporomandibular joint synovial lavage fluid of patients with closed lock.

AIMS: To investigate the presence of endogenous beta-endorphin, an opioid, in the synovial lavage fluid of the temporomandibular joint (TMJ), and to compare the concentration of 3-endorphin in patients with closed lock with that in symptom-free subjects. METHODS: Thirty-eight patients (38 joints) with closed lock diagnosed on the basis of the results of clinical examination and magnetic resonance imaging (MRI) and 11 healthy volunteers (19 joints) were examined. Samples of lavage fluid were obtained prior to arthrocentesis by washing the joint with saline. Samples were assayed for beta-endorphin by an enzyme immunoassay, and concentrations of protein were measured by a bicinchoninic acid assay. Subjective pain was assessed by patients using a visual analog scale. Bone changes in the condyle were assessed by MRI, and synovitis was assessed on the basis of arthroscopic findings. RESULTS: beta-endorphin was present in the synovial fluid of the TMJ, and the concentration was significantly higher in patients with closed lock of the TMJ compared to symptom-free volunteers. The beta-endorphin levels were not, however, significantly correlated with clinical parameters in the patients. CONCLUSION: The study results support recent findings that some opioids and their receptors exist not only within the central nervous system but also in the TMJ region, and that opioid concentrations are higher in patients with pain and dysfunction of the TMJ.