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Understanding matrix molecular activities that regulate the postnatal growth and remodeling of the temporomandibular joint (TMJ) articular disc and condylar cartilage will enable the development of effective regenerative strategies targeting TMJ disorders. This study elucidated the distinct roles of type V collagen (collagen V) in regulating these two units. Studying the TMJ of young adult Col5a1 +/- mice, we found that loss of collagen V resulted in substantial changes in the proliferation, clustering and density of progenitors in condylar cartilage, but did not have a major impact on disc cells that are more fibroblast-like. Although loss of collagen V led to thickened collagen fibrils with increased heterogeneity in the disc, there were no significant changes in local micromodulus, except for a reduction at the posterior end of the inferior side. Following the induction of aberrant occlusal loading by the unilateral anterior crossbite (UAC) procedure, both wild-type (WT) and Col5a1 +/- condylar cartilage exhibited salient remodeling, and Col5a1 +/- condyle developed more pronounced degeneration and tissue hypertrophy at the posterior end than the WT. In contrast, neither UAC nor collagen V deficiency induced marked changes in the morphology or biomechanical properties of the disc. Together, our findings highlight the distinct roles of collagen V in regulating these two units during postnatal growth and remodeling, emphasizing its more crucial role in condylar cartilage due to its impact on the highly mechanosensitive progenitors. These results provide the foundation for using collagen V to improve the regeneration of TMJ and the care of patients with TMJ disorders. STATEMENT OF SIGNIFICANCE: Successful regeneration of the temporomandibular joint (TMJ) articular disc and condylar cartilage remains a significant challenge due to the limited understanding of matrix molecular activities that regulate the formation and remodeling of these tissues. This study demonstrates that collagen V plays distinct and critical roles in these processes. In condylar cartilage, collagen V is essential for regulating progenitor cell fate and maintaining matrix integrity. In the disc, collagen V also regulates fibril structure and local micromechanics, but has a limited impact on cell phenotype or its remodeling response. Our findings establish collagen V as a key component in maintaining the integrity of these two units, with a more crucial role in condylar cartilage due to its impact on progenitor cell activities., Competing Interests: Declaration of competing interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objectives: This study aimed to determine the effects of chronic intermittent hypoxia (CIH) and stress change (SC) on the development of the condyle in mouth breathing rats., Design: A total of 120 4-week-old rats were randomly assigned to one of five groups. The control (Ctrl) group was the blank control and the intermittent nasal obstruction (INO) group was the positive control. Mild CIH (mCIH) and severe CIH (sCIH) groups were developed by adjusting environmental oxygen concentration and monitoring real-time blood oxygen saturation (SpO 2 ). The SC group was developed using INO, increased environmental oxygen concentration, and real-time SpO 2 monitoring. Six rats from each group were sacrificed for analysis at 0, 1, 2, or 4 weeks., Results: Similar to the INO group, condyle and mandibular body development in the sCIH group, but not in the mCIH group, was significantly inhibited compared with the Ctrl group. The SC group had inhibited development of the condyle, especially of the posterior zone, but had minimal impact on the growth of the mandible., Conclusion: The inhibitory effects of CIH on the development of the condyle and mandibular body were SpO 2 -dose-dependent. When SC occurred, inhibited development was observed in the posterior zone of condyle but not the whole mandible. These findings provide important insights for targeted interventions that address the consequences of mouth breathing in children., Competing Interests: Declaration of Competing Interest The authors declare no potential conflicts of interest with respect to the authorship and publication of this article., (Copyright © 2024. Published by Elsevier Ltd.)

Background: Adolescents with temporomandibular joint (TMJ) anterior disk displacement (ADD) frequently develop dentofacial deformities. It is unknown whether adjunctive arthroscopic diskopexy compared with orthodontic treatment alone increases condylar growth and then improves dentofacial deformity. This study aimed to determine whether arthroscopic diskopexy before functional appliance (joint-occlusal treatment) or single functional appliance (occlusal treatment) increases condylar growth and improves dentofacial deformity among adolescents with TMJ ADD., Methods: A multicenter, randomized, parallel, controlled trial was conducted in 3 centers in China. Adolescents diagnosed with TMJ ADD and dentofacial deformity were enrolled. Eligible participants were randomly assigned to a joint-occlusal group or occlusal group at a ratio of 2:1. Magnetic resonance imaging scans and cephalometric radiographs were evaluated at baseline, at 8 months, and at 14 months. The primary outcome was changes in condylar height from 14 months to baseline. Secondary outcomes were changes in skeletal position., Results: A total of 240 patients (14.65 ± 1.88 years of age) were randomized (joint-occlusal group, 160; occlusal group, 80). The overall difference in condylar height between groups was 3.65 mm (95% CI, 3.10 to 4.19 mm; P < 0.001). The between-group differences in condylar height on the left and right sides were 3.60 mm (95% CI, 2.92 to 4.28 mm; P < 0.001) and 3.69 mm (95% CI, 3.06 to 4.32 mm; P < 0.001), respectively. Significant between-group differences were noted in skeletal position (all P < 0.001)., Conclusion: Joint-occlusal treatment can promote condylar growth and improve dentofacial deformity in adolescents after 14 months when compared with single occlusal treatment., Clinical Question/level of Evidence: Therapeutic, I., (Copyright © 2023 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the American Society of Plastic Surgeons.)

Background: Forensic age estimation is a procedure which utilises many methods to estimate the age of both living and deceased individuals, including those who have died in natural disasters or man-made catastrophes. The pattern and closure of spheno-occipital synchondrosis (SOS) fusion, along with subchondral ossification of the mandibular condyle, can be used to estimate age., Aim and Objectives: This study aims to estimate age using computed tomographic (CT) images of spheno-occipital synchondrosis fusion (SOS) and mandibular condylar cortication (MCC), and to correlate these findings with chronological age., Materials and Methods: The present study included 435 CT images of individuals aged 10-25 years. SOS fusion was assessed using a four-stage system, and MCC was assessed bilaterally using a three-stage system on the sagittal plane. Data on fusion stages and cortication types were entered along with chronological age, and then statistically analysed., Results: SOS fusion stage 2 occurred at similar age in males (19.82 ± 2.67 years) and females (19.23 ± 2.93 years). Earlier fusion of other stages was observed in females by a mean age of 2 years. MCC was completed 1 year earlier in females, with statistically significant differences (p ≤ 0.001). When comparing cortication types and different fusion stages, only type II cortication showed statistically significant differences compared to different fusion stages (p ≤ 0.001)., Conclusion: Mandibular condylar cortication (MCC) and spheno-occipital synchondrosis (SOS) fusion were positively correlated with chronological age, suggesting that these parameters can be used as an adjunct method for age estimation., Competing Interests: The authors report no conflicts of interest in this work., (Copyright© 2024 IOFOS This work is published and licensed by International Organization for Forensic Odonto-Stomatology.)

Objective: The aim of this study was to understand the temporal and spatial distribution of canonical endochondral ossification (CEO) and non-canonical endochondral ossification (NCEO) of the normal growing rat condyle, and to evaluate their histomorphological changes following the simultaneous hypotrophy of the unilateral masticatory closing muscles with botulinum toxin (BTX)., Design: 46 rats at postnatal 4 weeks were used for the experiment and euthanized at postnatal 4, 8, and 16 weeks. The right masticatory muscles of rats in experimental group were injected with BTX, the left being injected with saline as a control. The samples were evaluated using 3D morphometric, histological, and immunohistochemical analysis with three-dimensional regional mapping of endochondral ossifications., Results: The results showed that condylar endochondral ossification changed from CEO to NCEO at the main articulating surface during the experimental period and that the BTX-treated condyle presented a retroclined smaller condyle with an anteriorly-shifted narrower articulating surface. This articulating region showed a thinner layer of the endochondral cells, and a compact distribution of flattened cells. These were related to the load concentration, decreased cellular proliferation with thin cellular layers, reduced extracellular matrix, increased cellular differentiation toward the osteoblastic bone formation, and accelerated transition of the ossification types from CEO to NCEO., Conclusion: The results suggest that endochondral ossification under loading tended to show more NCEO, and that masticatory muscular hypofunction by BTX had deleterious effects on endochondral bone formation and changed the condylar growth vector, resulting in a retroclined, smaller, asymmetrical, and deformed condyle with thin cartilage., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Sang-Hwy Lee has patent #Korean patent 10–2024-0006750 pending to Sang-Hwy Lee. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Introduction: Transdifferentiation of chondrocytes into bone cells explains most condylar growth during prenatal and early postnatal stages, but the mechanisms regulating chondrocyte transdifferentiation during late postnatal growth remain unknown. This study aimed to quantify the effects of dietary loading on chondrocyte-derived osteogenesis during late postnatal condylar growth., Methods: Two compound mouse lines were used to trace the fate of chondrocyte lineage in vivo. Twelve 3-week-old male Aggrecan-Cre ERT2 (Acan Lineage ); R26R TdTomato ; 2.3 Col10a1-GFP and twelve 3-week-old male Col10a1-Cre (Col10a1 Lineage ); R26R TdTomato ; 2.3Col1a1-GFP were randomly divided into experimental (soft-food diet, n = 6) and control (hard-food diet, n = 6) groups and kept for 6 weeks. One time, tamoxifen injections were given to Acan Lineage mice at 3 weeks. Radiographic, microcomputed tomographic, and histomorphometric analyses were performed., Results: Radiologic analysis showed that mice with a soft-food diet had smaller mandible lengths as well as decreased bone volume and density for their condylar process. Histologically, mice with soft diets had reduced activity in chondrocyte proliferation and maturation compared with the controls. Cell lineage tracing results showed the number of Acan Lineage -derived bone cells (293.8 ± 39.8 vs 207.1 ± 44.6; P = 0.005), as well as total bone cells (445.6 ± 31.7 vs 360.7 ± 46.9; P = 0.004), was significantly higher in the hard-diet group than in the soft-diet group, whereas the number of non-Acan Lineage -derived bone cells was not significantly different among groups (P = 0.938). Col10a1 Lineage mice showed the same trend., Conclusions: Dietary loading directly affects condyle chondrogenesis and chondrocyte transdifferentiation, which alters the extent of condylar growth and remodeling., (Copyright © 2024 American Association of Orthodontists. Published by Elsevier Inc. All rights reserved.)

Objective: Fibroblast growth factors (FGFs) are a family of 22 proteins and 4 FGF receptors (FGFRs) that are crucial elements for normal development. The contribution of different FGFs and FGFRs for the homeostasis or disease of the cartilage from the mandibular condyle is unknown. Therefore, our goal was to characterize age-related alterations in the protein expression of FGF ligands and FGFRs in the mandibular condyle of mice., Method: Mandibular condyles of 1-, 6-, 12-, 18-, and 24-month-old C57BL/6J male mice (5 per group) were collected and histologically sectioned. Immunofluorescence for FGFs that have been reported to be relevant for chondrogenesis (FGF2, FGF8, FGF9, FGF18) as well as the activated/phosphorylated FGFRs (pFGFR1, pFGFR3) was carried out., Results: FGF2 and FGF8 were strongly expressed in the cartilage and subchondral bone of 1-month-old mice, but the expression shifted mainly to the subchondral bone as mice aged. FGF18 and pFGFR3 expression was limited to the cartilage of 1-month-old mice only. Meanwhile, pFGFR1 and FGF9 were mostly limited to the cartilage with a significant increase in expression as mice aged., Conclusions: Our results indicate FGF2 and FGF8 are important growth factors for mandibular condylar cartilage growth in young mice but with limited role in the cartilage of older mice. In addition, the increased expression of pFGFR1 and FGF9 and the decreased expression of pFGFR3 and FGF18 as mice aged suggest the association of these factors with aging and osteoarthritis of the cartilage of the mandibular condyle., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Purpose: To investigate the correlation between the occlusal canting and the bilateral temporomandibular joint (TMJ) space in adult and juvenile mandibular deviation patients and study the mutual influence between the occlusal canting and mandibular position, in order to provide references for clinical treatment., Methods: CBCT data of mandibular deviation patients（20 adults，20 juveniles）were selected. Inivo5 Dental Anatomage software was used to reconstruct the structures. The occlusal cant and vertical height of the bilateral maxillary from canines to first molars were measured, and the vertical heights difference between the same teeth on both sides was calculated. The anterior, superior and posterior space of temporomandibular joint were measured respectively in both groups. Pearson correlation analysis between the occlusal canting and bilateral condylar space was carried out by using SPSS 17.0 software package., Results: In the juvenile group, negative correlations were found between the occlusal cant and the superior TMJ space on the deviated side (P＜0.05). Negative correlation was found between the vertical height difference of bilateral canines and the anterior TMJ space on the deviated side in the juvenile group(P＜0.05). In the adult group, no significant correlation was observed among those correlated examination (P＞0.05)., Conclusons: The occlusal canting is moderately correlated with mandibular position in the early stage of mandibular deviation patients. Early treatment of mandibular deviation is of great importance in preventing its progression into severe skeletal malocclusion, and more attention should be paid on the correction of the canted frontal occlusion plane.

Background: Combined symphyseal-condylar mandible fractures are relatively common but difficult to manage in children. This study investigated the cause and management of symphyseal-condylar fractures in pediatric patients., Methods: This study presents a retrospective review and expert opinion of pediatric symphyseal-condylar mandibular fracture management at the authors' institution between 1990 and 2019. National data from the Healthcare Cost and Utilization Project Kids' Inpatient Database (2000 to 2016) were used to determine whether institutional data had national applicability., Results: Twenty-one patients at the authors' institution met inclusion criteria. Of these patients, 26.7 percent of deciduous dentition patients underwent open reduction and internal fixation, 40 percent underwent closed treatment (maxillomandibular fixation), and 33.3 percent received a soft diet. All mixed dentition patients underwent open reduction and internal fixation or closed treatment; all permanent dentition patients underwent open reduction and internal fixation. The national database (n = 1708) demonstrated similar treatment patterns: most permanent dentition patients (88.7 percent) underwent open reduction and internal fixation, most mixed dentition patients (79.2 percent) underwent closed treatment, and among deciduous dentition patients, 53.5 percent patients received a soft diet; 38 percent received closed treatment. In this study, the overall posttreatment complication rate was 62.5 percent among open reduction and internal fixation patients, 14.3 percent among closed treatment patients, and 16.7 percent among patients treated with a soft diet., Conclusions: Symphyseal-condylar mandibular fractures were associated with substantial morbidity in children. The authors created a treatment algorithm to maximize outcomes in children who suffer from this challenging fracture pattern., Clinical Question/level of Evidence: Therapeutic, III., (Copyright © 2021 by the American Society of Plastic Surgeons.)

Objective: Determine the role of the extracellular matrix protease ADAMTS5 in development of the trabeculated bone of the mandibular condyle., Methods: The mandibular condyles of wild type and mice deficient in the protease ADAMTS5 were examined for histopathology with Safranin O staining. Microcomputed tomography was performed to analyze the developing bone of the mandibular condyle. RNAscope and immunohistochemistry were utilized to investigate cell type and extracellular matrix expression., Results: Mice deficient in Adamts5, (Adamts5 tm1Dgen/J ) exhibit an increase in trabecular separation (n = 37 wild type; n = 27: P < 0.0001) and reduction of trabecular thickness P = 0.0116 and bone volume fraction P = 0.0869 in the mandibular condylar head compared to wild type littermates. The altered bone parameters were more pronounced in male Adamts5 -/- mice compared to female Adamts5 -/- mice (TbSp; P = 0.03). Adamts5 was co-expressed with versican and Gli1 in mesenchymal, stem-like cells in the transition zone where the trabeculated bone is adjacent to mature hypertrophic chondrocytes. Loss of Adamts5 caused a reduction of Bglap expressing osteoblasts throughout mandibular condylar development and in young adult mice. The protease Mmp13, that is involved in mineralization and is expressed by hypertrophic chondrocytes and osteoblasts, was reduced in the mandibular condyle of Adamts5 deficient mice., Conclusion: This is the first report of a novel and critical role for Adamts5 in bone formation within the mandibular condyle of the temporomandibular joint. These data indicate Adamts5 may be required in the transdifferentiation of hypertrophic chondrocytes to osteoblasts during trabecular bone formation in development of the mandibular condyle., (Copyright © 2021 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

Purpose: This study aimed to quantify mandibular ramus height and condylar distances asymmetry indexes in adult patients with different vertical facial growth pattern using Cone Beam computed tomography (CBCT)., Methods: An observational cross-sectional study was conducted by using CBCT of 159 patients (mean age 26.36 ± 5.32 years). Vistadent 3D ® software was used to determine the facial pattern in 3 groups (N = 53): hypodivergent, normodivergent and hyperdivergent-by Ricketts VERT index. Mandibular ramus height and the condylar linear distance in relation to the median sagittal plane were evaluated. The asymmetry index was calculated considering the right and left sides. Data were analyzed by generalized linear models and Tukey post-hoc test (α = 0.05)., Results: Significantly lower values were found for the left and right mandibular ramus height in the hyperdivergent skeletal pattern (P < 0.05). There was no statistically significant difference for condylar and intercondylar distances among the facial groups (P > 0.05). Asymmetry indexes (mandibular ramus height and condylar distance) were similar, and no statistically significant differences were found among the skeletal patterns. In most subjects, the severity of mandibular ramus height asymmetry varied from light to not clinically significant independently of the facial type., Conclusion: The findings suggest that vertical facial growth pattern not affected the asymmetry index of mandibular ramus height and the intercondylar distance. The results also demonstrated significantly shorter mandibular ramus height for the hyperdivergent skeletal pattern individuals.

Objective: Thalassemia is the most common hereditary blood disorder across the world. This study aimed to identify some mandibular features of thalassaemic patients and compare them with unaffected counterparts., Material and Methods: This retrospective case-control study was carried out on lateral cephalograms of 60 subjects (26 males, 34 females) with class II malocclusion and age range of 11 to 15 years. The control group consisted of 60 non-thalassaemic subjects with class II malocclusion and similar chronological age, gender and vertical facial dimension. Based on the Jarabak index, the case and control subjects were classified into hyperdivergent, normodivergent and hypodivergent growth patterns. Four linear (ramus height, ramus width, mandibular depth, and antegonial notch depth) and 3 angular (symphyseal angle, gonial angle, and mandibular arc angle) cephalometric parameters were measured to represent mandibular morphology. The data were analysed using Chi-square test and Student's t-test., Results: No significant difference was found in linear measurements between thalassaemic patients and controls. The symphysis angle was significantly greater and the mandibular arc angle was significantly smaller in the total thalassaemic sample than the control individuals (P<0.001 and P=0.004, respectively). The difference in symphysis angle was significant in both hyperdivergent and normodivergent subjects (P=0.004 and P=0.002, respectively), whereas the difference in mandibular arc angle was only significant in the normodivergent subgroup P=0.001)., Conclusions: The smaller mandibular arc angle in the thalassaemic sample suggests a more superior than posterior growth direction of condyles compared with healthy individuals. The difference in symphyseal angle represents inherent differences in chin morphology between thalassaemic subjects and controls., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Purpose: Mandibular condyle development can be evaluated with radiographic evaluation of subchondral cortical bone. The aim of this study is to investigate mandibular condyle cortication (MCC), articular eminence cortication (AEC) and mandibular cortical index (MCI) according to age and gender on CBCT, and relationship between each other., Methods: CBCT scans of 520 patients (312 male and 208 female, age range 7-84) were retrospectively investigated to evaluate MCC, AEC and MCI. MCC and AEC were examined in sagittal section and MCI in panoramic reformatted image. MCC and AEC were classified as Type I, Type II and Type III according to density difference between the cortical bone enclosing condyle and articular eminence. Categorical variables were tested by Chi square., Results: When MCC, AEC and MCI were compared, a significant relationship was detected (p < 0.05). According to age, there was a significant difference between MCC, MCI and AEC types with each other (p < 0.05). No significant discrepancy was found between gender and MCC, AEC and MCI (p > 0.05)., Conclusions: This study evaluated the distribution of MCC, AEC, MCI according to age and gender and detected that these cortications were correlated. This result may be caused by anatomical proximity bone components and functional stimuli. Knowledge of these cortications can be important for accurate diagnosis of TMJ disorders and may also be helpful for prediction of osteoporotic changes.

MicroRNA (miRNA) are a class of small non-coding single-stranded RNA that exert their biological effects by binding to target messenger RNA (mRNA). There is new evidence that miRNA may play an important role in regulating the growth and development of mandibular condylar cartilage. In this paper, the production and mechanism of miRNA are reviewed, and the progress of studies on the growth and development of mandibular condylar cartilage, which is helpful to further study the growth and development of mandibular condylar cartilage.

Objective: The temporomandibular joint (TMJ) displays a high remodelling capability in response to occlusion changes. The purpose of the current study was to investigate the responses of TMJ condyles of growing mice to the installation of a unilateral anterior crossbite (UAC) prosthesis and the replacement of the UAC prothesis with a bilateral anterior elevation (BAE) prosthesis., Materials and Methods: C57BL/6J mice were randomly assigned to the blank control and experimental groups. In mice in the experimental groups, UAC was created, while in others, BAE was created after the creation of UAC or removal of UAC. Changes in TMJ condylar cartilage and subchondral bone were assessed., Results: The degradation of condylar cartilage induced by UAC was reversed by BAE, as evaluated by cartilage histochemical changes, collagen II-positive area, collagen X-positive chondrocytes and expression levels of Adamts-5, Mmp13, Tnf-α and Il-1β. Subchondral bone was assessed based on the subchondral bone volume, the number of TRAP-positive cells and the Opg/Rankl ratio., Conclusion: The growing mouse TMJ condyle displays a high remodelling capability, which can be degenerative or rehabilitative in response to the creation of UAC and the replacement of UAC with BAE. Early correction of occlusion is beneficial for the recovery of degenerative condyles., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. All rights reserved.)

Objective: We evaluated the effects of photobiomodulation (PBM), mandibular advancement (MA), and the combination of both treatments (PBM+MA) on condylar growth, by the analysis of cartilage and bone formation, fibrillar collagen deposition, proteoglycan content, cell proliferation, and clastic cell index (CCI). Methods: Forty male Wistar rats were randomly assigned to CONTROL, PBM, positive control-MA, and PBM+MA groups. The appliance was worn 10 h/day. Laser was irradiated bilaterally on mandibular condyles in 8 alternate days (1 irradiation point per condyle) using the following parameters: 780 nm, 10 J/cm 2 , 40 mW, 1 W/cm 2 , 10 sec/point, 0.4 J/point, and cumulative dose per point: 3.2 J. PBM+MA received both treatments simultaneously. After 15 days, the animals were euthanized and the condyles dissected and embedded in paraffin. Histological sections from the intermediate portion of the condyle were used for morphometric analysis. The relative frequency (%) of fibrillar collagens was determined in sections stained with picrosirius red-hematoxylin under polarized light or Gömöri's method for reticular fibers. Proteoglycan content was evaluated by computerized photocolorimetric analysis. CCI was determined by tartrate-resistant acid phosphatase (TRAP), and proliferating cell nuclear antigen (PCNA) was detected by immunohistochemistry. Results: PBM and MA influenced condylar cartilage thickeness and matrix deposition, but none of the treatments affected significantly the area of the condyle. CCI were not influenced by the treatments, but clastic cells distribution was influenced by MA and PBM+MA treatments. There was no significant difference in proliferating cells among the groups. Conclusions: This study demonstrated that PBM and MA stimulates matrix deposition and cartilage thickening in the mandibular condyle, but was not able to demonstrate a synergistic effect between the treatments. Additional studies should be conducted to evaluate the possible synergistic effect between PBM and MA.

Introduction: The purpose of this study was to examine growth-promoting effects of myo-inositol nutritional supplementation on the mandible in experimental animals., Methods: Mice were fed on diets that contained various concentration of myo-inositol for 3 to 12 weeks. The length of the mandible, maxilla, and femur were measured on μCT images. The mandible and tibia were examined histologically and immunohistochemically. The effects of myo-inositol on cell proliferation and chondrocytic differentiation were examined using ATDC5 cells., Results: Myo-inositol supplementation had no effects on body weight, length, and maxilla and femur lengths. However, the length of mandible and the thickness of the mandibular condylar cartilage (MCC) were increased by myo-inositol supplement. Microarray analysis revealed that Pik3cd was highly expressed in MCC as compared to that in the cartilage of the tibial growth plate, which was confirmed by real-time RT-PCR and immunohistochemistry. ATDC5 cells also highly expressed Pik3CD. Myoinositol induced increases in cell proliferation and chondrocytic differentiation in ATDC5 cells. The addition of a PIK3CD inhibitor blocked the induction of cell proliferation by myo-inositol in ATDC5 cells., Conclusions: Nutritional supplementation with myo-inositol in growing mice augmented mandibular endochondral growth without any systemic effects. The specific promotion of mandibular growth by myoinositol is primarily dependent on the specific intensive expression of PIK3CD in the MCC., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: To evaluate the effect of sympathetic nervous system hyperactivity on craniofacial skeletal growth in growing spontaneously hypertensive rats (SHRs)., Design: Craniofacial skeletal growth was compared between male SHR and Wistar-Kyoto rats (WKR) using linear measurements on lateral and transverse cephalometric radiographs at the age of 12 weeks. Tibia length was measured as an index of whole body growth. Body weight　and blood pressure were measured from 3 to 12 weeks of age. Bone microstructure in the mandibular condyle and tibia between the two groups was compared at the age of 12 weeks using microcomputed tomography., Results: The SHRs had a significantly lower body weight than WKRs from 7 weeks of age, and tibial length was significantly smaller in the SHRs than in the WKR at 12 weeks of age. In all SHRs, blood pressure was significantly higher than in WKRs from 3 to 12 weeks of age. Cephalometric analyses revealed decreased measurements of the neurocranium, viscerocranium, and mandible in SHRs, and mandibular growth was most negatively affected in this group. Lastly, in SHRs, microcomputed tomography analyses revealed decreased bone mineral density and bone volume/tissue volume in the mandibular condyle but not in the tibia., Conclusion: In growing SHRs, hypertension related to the hyperactivity of the sympathetic nervous system reduced craniofacial skeletal growth more than the growth of the tibia., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Objective: The aim of this study is to elucidate the local effects of fibroblast growth factor 23 (FGF23) in on mandibular condylar growth in growing rats., Design: Growing Sprague-Dawley rats received intra-temporomandibular joint injections of phosphate buffer solution (PBS), adenovirus-mediated green fluorescent protein (Ad-GFP) or adenovirus-mediated fibroblast growth factor 23 (Ad-FGF23), which were marked as groups A, B, and C, respectively. In vitro, we treated rat mandibular cartilage chondrocytes with PBS, Ad-GFP, and Ad-FGF23., Results: The mandibular condyles in group C grew smaller sizes than those in the other control groups due to significant differences among the experimental and control groups with the value of C-D, Q-R (P ≤ 0.05), accompanied by diminished bone mass of sub-cartilage condyles via micro CT analysis. Histologically, the length of the hypertrophic zone was diminished and was associated with decreasing chondrocyte proliferation in group C. Quantitative real-time PCR indicated significant decreases in the expression of chondrogenesis marker genes, including Type X collagen (Col X) and SRY-type box 9 (Sox 9). Moreover, elevated Ad-FGF23 suppressed chondrocyte proliferation and the expression of the chondrogenic differentiation markers Col X and Sox 9 of in vitro., Conclusions: Local injection of FGF23 suppressed the development and decreased the bone mass of condyles through the decreasing the formation of condylar cartilage, specifically by regulating condylar cartilage cell viability and chondrogenesis expression., (Copyright © 2018. Published by Elsevier Ltd.)

Aim: This study tests whether rapid maxillary expansion (RME) exerts long term effects on interglenoid fossa distance and condyle fossa relationship., Materials and Methods: Consecutive growing patients aged 8 to 13 years were allocated either to the RME group or control group. Cone-beam computed tomography was performed at baseline and at 6 months. Specific software was used to determine fixed landmarks. Multivariate Analysis of Covariance (MANCOVA) models were used, with time by group interaction, using age as a covariate., Results: Twenty-seven patients with a mean age of 11.4 ± 1.5 years were included. There was an overall significant group by time interaction (p = 0.012, effect size 0.59). Change in the lateral position of the glenoid fossa, the primary outcome, was reached (p = 0.008, effect size 0.258). Change in the laterolateral position of the center of the condyle, and the co-primary outcome was also significant (p = 0.011, effect size = 0.24). Nasal cavity width increased (p = 0.065, effect size = 0.14). There was an initial asymmetry in the horizontal position of the condyles that was carried on with no effect of RME., Conclusion: Rapid maxillary expansion (RME) produces a significant increase in the interglenoid fossa distance and displacement of the mandibular condyles at 6 months in growing patients compared to a control group., Clinical Significance: The current study shows that RME is effective during growth, widening the interglenoid fossa distance and the lateral positions of the condyles and eventually enlarging the nasal cavity, without causing asymmetry.

Objective: The aim of this systematic review was to provide a comprehensive synthesis of available evidence evaluating the effect of dietary loading on temporomandibular joint/condyle, condylar cartilage, alveolar bone of the mandible and the periodontal ligament in healthy mice and rats., Design: Medline via PubMed, EMBASE and Open Grey databases were searched for published and unpublished literature. Search terms included "mandiblular condyle", "alveolar bone", "temporomandibular joint", "condylar cartilage", "periodontal ligament", "rat", "mice". After data extraction, risk of bias (SYRCLE) and reporting quality (ARRIVE) were assessed. Random effects meta-analyses were performed for the outcomes of interest where applicable., Results: A total of 33 relevant articles were considered in the systematic review, while only 6 studies were included in the quantitative synthesis. Risk of Bias in all studies was judged to be unclear to high overall, while reporting quality was suboptimal. Comparing soft to hard diet animals, significantly reduced anteroposterior condylar length (4 studies, weighted mean difference: -0.40 mm; 95% CI: -0.47, -0.32; p < 0.001) and width (4 studies, weighted mean difference: -0.043 mm; 95% CI: -0.51, -0.36; p < 0.001) were found in rats. Decreased anteroposterior condylar dimensions were detected for mice as well (2 studies, weighted mean difference: -0.049; 95% CI: -0.56, -0.43; p < 0.001)., Conclusions: Overall, there was strong evidence to suggest a significant effect of soft diet on reduced condylar dimensions in rodents; however, there is need for further high quality experimental studies to inform current knowledge on condylar cartilage, alveolar bone and periodontal ligament related outcomes., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Background and Objectives: Apart from the primary effect of bite-blocks on tooth position, they may also influence the mandibular condylar growth. Our aim was to investigate their influence on the condylar morphology, with variable masticatory forces., Material and Methods: Fifty-two 4-week old male rats were divided into hard and soft diet groups in order to create individuals with different masticatory muscle capacity. Two weeks later, they were equally divided into bite-block and control groups. After a total of 6 weeks experimental time, the animals were sacrificed. The mandibles were scanned with high-resolution micro-CT and 3D analysis was performed on the condylar neck and head of the condyle. The volume and the length of the condylar process were measured. Statistical analysis was done with a one-way analysis of variance., Results: The use of bite-blocks decreased the length of the condylar process (P = 0.001) as well as the volume of the condylar neck (P = 0.001) and head (P = 0.006). The soft diet decreased the volume of the condylar neck (P < 0.001) and head (P < 0.001) two to three times more than the bite-blocks but did not affect the condylar process length. The interaction between the two variables was not statistically significant., Conclusions: Both the bite-block appliance and weak masticatory muscle function reduced the volume at all regions of the condylar process, although the functional factor had a substantially greater effect. However, only the bite-block appliance affected the condylar process length. In the presence of both factors, an additive effect was found but no interaction detected.

Objective: To investigate the influence of condylar fractures on the growth of condylars after conservative treatments by three-dimensional measurement. Methods: Twenty three children with unilateral condylar fracture followed-up for at least 1 year in Shanghai Ninth People's Hospital were included from June 2016 to March 2017. CT scans were performed for each patient. Three-dimensional virtual skulls were reconstructed and measuring points were defined with Simplant 11.04 software. The depth of glenoid fossa, height of articular eminence, width, height and depth of condylar, deviation of pogonion were measured. Statistical analyses were conducted to assess difference between the bifid group and the normal group. Results: No difference was observed in the vertical position of crest of the articular eminence between two groups ( P =0.110). The vertical position of roof of the glenoid fossa in bifid side was significantly superior than the one in normal side ( P =0.010). Bifid side had a shorter ( P =0.002) and wider( P =0.002) condylar than normal side did. No difference was observed in the depth of condylar between two groups ( P =0.071). The average deviation of pogonion was (0.69±1.75) mm ( P =0.072) from sagittal plan. Conclusions: This short-termed study indicates that children's growth potential of condylar is under average after conservative treatments. Because the bone hyperosteogeny of glenoid fossa compensates the hypotrophy of condylar, no deviation of pogonion is detected.

Objective: Secondary cartilage develops from osteochondral progenitor cells. Hypertrophic chondrocytes in secondary cartilage increase within a very short time and then ossify rapidly. In the present study, we investigated the sequential development process of osteochondral progenitor cells, and the morphology and size of hypertrophic chondrocytes in secondary cartilage., Design: ICR mice at embryonic days (E) 14.5-17.5 were used. The mandibular condyle and the medial pterygoid process of the sphenoid bone were observed as secondary cartilage, and the cranial base and the lateral pterygoid process of the sphenoid bone, which is primary cartilage, were observed as a control. Thin sections were subjected to immunostaining and alkaline phosphatase (ALP) staining. Using a confocal laser microscope, 3D stereoscopic reconstruction of hypertrophic cells was performed. To evaluate the size of hypertrophic chondrocytes objectively, the cell size was measured in each cartilage., Results: Hypertrophic chondrocytes of secondary cartilage first expressed type X collagen (Col X) at E15.5. SRY-box 9 (Sox 9) and ALP were co-expressed in the fibroblastic/polymorphic tissue layer of secondary cartilage. This layer was very thick at E15.5, and then rapidly became thin. Hypertrophic cells in secondary cartilage were markedly smaller than those in primary cartilage., Conclusions: The small hypertrophic cells present in secondary cartilage may have been a characteristic acquired in order for the cartilage to smoothly promote a marked increase in hypertrophic cells and rapid calcification., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Purpose: The aim of the present study is to evaluate the relationship between mandibular condyle cortication and chronologic age and gender via cone-beam computed tomography (CBCT) and to investigate the effectiveness of using the condylar cortication as a new method of age estimation., Methods: CBCT images from 433 subjects aged 8 to 31 years were included in this study. The right and left condyle cortication were assessed on the sagittal plane separately for each individual by the same investigator via a new method that describes the cortication of the condyle. Type I: There is no cortication on the condyle. Type II: The bone that is on the superior surface of the condyle is seen less density than the structures around the condyle. Type III: The surface of the condyle is seen similar or higher density than the surrounding cortical areas., Results: The type of the condyle cortication in the right and left mandible was similar for almost each subject and there was no statistically significant different between them (p = 0.375). When we evaluated the results without including these patients for male, Type I cortication of the condyle was seen at 14.14 ± 2.3 years, Type II cortication of the condyle was seen at 16.11 ± 3.18 years and Type III cortication of the condyle was seen at 19.39 ± 3.96 years. For the female, Type I cortication of the condyle was seen at 13.01 ± 2.16 years, Type II cortication of the condyle was seen at 15.52 ± 2.71 years and Type III cortication of the condyle was seen at 17.95 ± 3.13 years. The minimum age of Type III cortication was 11 and 15 years old for male and female, respectively. However, there are subjects, who are 30 year old man and 31 year old female, have no cortication as much as similar or higher than the surrounding the cortical areas., Conclusion: This study is the first investigation of the relationship between condyle cortication and chronologic age with CBCT in the Turkish population. The type of cortication in the right and left condyle may be different for the same individual. Chronologic age increased as the stages of the cortication process from Type I to Type III in male and female individuals, and all the stages of the cortication in the mandibular condyle of male occur later time according to female., (Copyright © 2018 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.)

This report presents a follow up of a clinical case published five years ago by the same authors. In the previous report, the authors showed a young girl treated with a myofunctional appliance due to a mandibular condylar agenesia. After a traditional graft had failed, the patient successfully responded to the functional treatment by forming a mandibular condyle. In this new report, the authors are showing how the mandibular condyle has continued developing within normal limits and, the mandibular ramus has continued positively remodeling. The bone biology embedded in the biological process reported here is discussed by the authors.

Background: In the present paper, the authors analyze the effect of the "Swallowing Occlusal Contact Intercept Appliance" (SOCIA) in treatment of children with hyperdivergent Class II malocclusion. This functional appliance has no intra-oral anchorage, but induces a continuous periodontal, muscular, and articular stimulation., Methods: Twenty-six patients with hyperdivergent growth and class II malocclusion were selected and treated with SOCIA appliance. Cephalometric analysis was performed before treatment (T1) and immediately after the treatment (T2)., Results: After 24 months treatment authors observed a modification of maxillary growth with a reduction of the divergence with an increase of the posterior facial height, a modification of condylar inclination and forward position of the a hyoid. No modifications was observed about the ANB angle. After treatment the open bite was resolved with a reduction of the inclination of the upper incisors., Conclusions: SOCIA is a reliable functional appliance in growing age patients with a hyperdivergent pattern growth, anterior open bite and class II molar malocclusion.

Mandibular hypoplasia is a common jaw deformity that affects breathing, occlusal function and facial aesthetics. Stimulating mandibular condylar growing with functional appliances is an ordinary but controversial treatment method in orthodontics. Therefore, it is vital to clarify how functional appliances affect condylar growing. Raf-1 kinase inhibitor protein (RKIP), as an endogenous inhibitory molecule of the ERK signaling, is postulated to involve in stress-induced response to articular cartilage. This study was to reveal the role of RKIP in regulating cartilage matrix synthesis with functional appliance treatment. Here, position rat mandibular forward simulating functional appliance effect to examine the stress-induced modification of mandibular condylar in vivo, meanwhile rat mandibular condylar chondrocytes (Mccs) were subjected to cyclic tensile stress (CTS, 16%, 1 HZ). The results showed that mandibular forward therapy enhanced condylar cartilage growth. The thicknesses of all layers of condylar cartilage were increased significantly. RKIP expression was also increased in the mature cartilage layer. In addition, CTS could enhance extracellular matrix formation and cartilage marker expression (aggrecan and collagen II), which shared a similar expression pattern with RKIP in Mccs. However, CTS induced up-regulation of collagen II and aggrecan was blocked by RKIP knockdown. Nuclear p-ERK, targeting downstream of RKIP, showed a decrease after CTS,which was disappeared in RKIP-knockdown Mccs. Taken together, physiological mechanical stimulation promotes cartilage growth modification by up-regulating RKIP through inhibiting ERK signaling pathway.

Condyle is a critical growth region of the mandible where mandible by endochondral ossification occurs. Condylar cartilage belongs to the secondary cartilage, which is not only affected by genetic factors but also by stress, drug intake, and other local factors. To promote the growth of the mandible, various exogenous and local factors were used to alter the biological environment of the condylar cartilage to stimulate endochondral ossification. This article reviews studies on the influence of exogenous factors on condylar growth and reconstruction. This literature review will provide a reference point for the treatment of patients with mandibular retraction.

Objective: To assess the mandibular condylar growth using cone-beam CT (CBCT) in beagle dogs treated with Herbst appliance and exogenous prostaglandin E2 (PGE2) during late stage of growth. Methods: Twenty-four male beagle dogs aged 8 months were divided into four groups according to the random number table ( n= 6 in each group): natural growth group, mandibular protraction group (Herbst group), injected prostaglandin E2 group (PGE2 group), mandibular protraction plus injected prostaglandin E2 group (Herbst+PGE2 group). The beagle dogs in Herbst+PGE2 group and PGE2 group were injected 0.1 ml of prostaglandin E2 (dose of 0.05 mg) into bilateral temporomandibular joint articular cavity. The dogs in natural growth group and Herbst group were injected 0.1 ml of saline into bilateral temporomandibular joint articular cavity as control. PGE2 and saline were injected once every 3 days for 60 days, respectively. CBCT was taken before the application of Herbst appliance and after removal of the appliance for all beagle dogs in four groups at the same time. The CBCT images were reconstructed using Invivo5 software and the relevant parameters of temporomandibular joint were measured. Results: No significant difference was found in natural growth group before and after the experiment ( P> 0.05). After the treatment, the condylar height and condylar size in Herbst group ([0.19+0.04] and [0.18+0.30] mm), PGE2 group ([0.38+0.14] and [0.51+0.24] mm) and Herbst+PGE2 group ([0.65+0.08] and [0.70+0.24] mm) slightly increased ( P< 0.05). The condylar changes in all experimental groups were greater than the natural growth group ( P< 0.05), and the ranges of change, in descending order, were Herbst+PGE2 group, PGE2 group and Herbst group ( P< 0.05). However, the condylar longitudinal distances, condyle width, condylar transverse diameter, glenoid fossa width and glenoid fossa depth had no statistically significant difference among the four groups ( P> 0.05). Conclusions: Injection of exogenous PGE2 into the temporomandibular joint articular cavity, or using Herbst appliance separately, a certain amount of growth was observed on the mandibular condyle in beagle dogs during late stage of growth. The combination of Herbst appliance and exogenous PGE2 injection made the condylar growth more obviously.

There is a growing body of evidence supporting the involvement of the Wnt signaling pathway in various aspects of skeletal and joint development; however, it is unclear whether it is involved in the process of temporomandibular joint development. In order to clarify this issue, we examined the spatio-temporal distribution of mRNAs and proteins of the Wnt family during the formation of the mandibular condylar cartilage at the prenatal and postnatal stages. An in situ hybridization test revealed no mRNAs of β-catenin and Axin2 during early mesenchymal condensation; the ligands surveyed in this study (including Wnt-4, 5a, and 9a) were clearly detected at various ranges of expression, mainly in the condylar blastema and later distinct cartilaginous layers. Apart from β-catenin and Axin2, the Wnt family members surveyed in this study, including Lef-1, were found to be immunopositive during early chondrogenesis in the condylar cartilage at E14.5. After distinct chondrocyte layers were identified within the cartilage at E16.5, the expression of the Wnt signaling members was different and mainly restricted to proliferating cells and mineralized hypertrophic chondrocytes. In the adult mandibular condylar cartilage, the Wnt-4 mRNA, as well as the Wnt-4 and Wnt-9a proteins, was not observed. Our findings demonstrated that the Wnt signaling pathway was associated with the development of mandibular condylar cartilage., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objective: Mandibular distraction surgery is a critical treatment for jaw deformity. However, abnormal mandibular condylar bone resorption is often seen as complication after surgery. Our previous study using a rat mandibular distraction model suggested that overloading leads to mandibular condylar resorption. Host factors are also believed to influence the resorption. To understand the relationship between host factors and resorption, we investigated the effect of changing bone mass and architecture on the mandibular condyle using FK506., Study Design: FK506, an immunosuppressant, was used to compromise bone mass and architecture in this study. Animals were divided into 4 groups: distraction surgery (Dist), FK506 administration (FK), distraction surgery with FK506 administration (FK + Dist), and no surgery or FK506 administration (Cont)., Results: The FK group showed reduced bone mass and impaired bone architecture. The Dist group exhibited abnormal bone resorption on the surface of the condyles, which was slightly exacerbated in the FK + Dist group. Bone defect length decreased over time as a result of bone apposition in the Dist group. However, in the FK + Dist group, the bone defect length remained the same., Conclusions: These results suggest that bone mass and architecture strongly affect the tolerance to the overloading and adaptation with bone apposition in condylar resorption site., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: In the appendicular skeleton, estrogen via ERα signalling has been shown to mediate endochondral growth plate fusion in both males and females. However, the role of ERα in mediating growth of the mandibular condylar cartilage is unknown. Thus, this study focuses on the characterization of the mandibular condylar cartilage phenotype in young and adult male ERαKO mice., Setting: Columbia University Medical Center., Material and Methods: WT and ERαKO C57BL/6 male mice were sacrificed at 49 days or 9 months for phenotypic analysis. Changes to MCC thickness, cell number and cell density were measured using histomorphometric methods. Cartilage-specific gene expression and OARSI scores were investigated for 49-day and 9-month-old male ERαKO and WT mice., Results: In young mice, a significant increase in the number of mandibular condylar cartilage cells and a significant decrease in the expression of Col10, Runx2 and DMP1 were observed in the male ERαKO mice compared to WT. In 9-month-old mice, we found a similar increase in the number of cells but no change in osteoarthritic histological scoring in ERαKO mice compared to WT mice., Conclusion: In summary, estrogen plays a role in mediating mandibular condylar maturation in young male mice. However, according to this study, it does not play a role in mediating long-term growth or age-related mandibular condylar cartilage degeneration in males., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objective: To investigate the effect of different mechanical loading on the expression of Notch-1, Notch-3, Jagged-1 and Delta-like-1 in growing rabbits' condylar cartilage. Methods: Sixty-four ten-days-old rabbits were randomly divided into experimental and control groups. The rabbits in the experimental groups were fed on a powder diet, while the control groups were fed on a solid diet. The animals were sacrificed after 2, 4, 6 and 8 weeks. Notch-1, Notch-3, Jagged-1 and Delta-like-1 gene and protein expressions were examined by HE, immunohistochemistry, Western blotting and quantitative real-time PCR. Results: At 2, 4, 6, 8 weeks, the anterior part of condylar cartilage in solid diet groups ([318.1±4.3], [342.4±2.6], [364.2±3.2], [380.7±6.0] mm, respectively) were thicker than those in powder diet groups ([275.4±2.6], [301.1±2.0], [322.3±3.3], [366.5±8.4] mm, respectively) ( P< 0.05). There was no significant difference between the two groups in the middle part ( P> 0.05). From 2 to 6 weeks, the posterior part of cartilage in solid diet groups ([444.1±1.5], [451.1±0.3], [476.4±5.7] mm, respectively) was thinner than those in power diet groups ([470.4±2.7], [494.3±2.9], [512.3±5.7] mm, respectively) ( P< 0.05). At 6 weeks, there were more mRNA expressions of Notch-3, Jagged-1 and Delta-like-1 in solid diet group than in power diet group ( P< 0.05). The Notch-1 protein could be found in all layers of condylar cartilage, especially in the surface of hypertrophic zone. The expressions of Notch-1, Notch-3, and Delta-like-1 protein were increased from 2 to 6 weeks, and decreased at 8 weeks. In solid diet groups, the protein expressions of Notch-1 (at 2, 4, 6, 8 weeks), Notch-3 (at 2, 4, 6 weeks), Jagged-1 (at 2, 4, 6 weeks) and Delta-like-1 (at 4, 6, 8 weeks) were greater than in power diet groups ( P< 0.05). Conclusions: Low masticatory loading may delay or inhibit the development of condylar cartilage and its growing factors such as Notch-1, Notch-3, Jagged-1 and Delta-like-1. Appropriate masticatory loading plays an important role in normal development of the condyle.

As muscle activity during growth is considerably important for mandible quality and morphology, reducing dietary loading directly influences the development and metabolic activity of mandibular condylar cartilage (MCC). However, an overall investigation of changes in the protein composition of MCC has not been fully described in literature. To study the protein expression and putative signaling in vivo, we evaluated the structural changes of MCC and differentially expressed proteins induced by reducing functional loading in rat MCC at developmental stages. Isobaric tag for relative and absolute quantitation-based 2D nano-high performance liquid chromatography (HPLC) and matrix-assisted laser desorption/ionization time-of-flight/time-of-flight (MALDI-TOF/TOF) technologies were used. Global protein profiling, KEGG and PANTHER pathways, and functional categories were analyzed. Consequently, histological and tartrate-resistant acid phosphatase staining indicated the altered histological structure of condylar cartilage and increased bone remodeling activity in hard-diet group. A total of 805 differentially expressed proteins were then identified. GO analysis revealed a significant number of proteins involved in the metabolic process, cellular process, biological regulation, localization, developmental process, and response to stimulus. KEGG pathway analysis also suggested that these proteins participated in various signaling pathways, including calcium signaling pathway, gap junction, ErbB signaling pathway, and mitogen-activated protein kinase signaling pathway. Collagen types I and II were further validated by immunohistochemical staining and Western blot analysis. Taken together, the present study provides an insight into the molecular mechanism of regulating condylar growth and remodeling induced by reducing dietary loading at the protein level.

Objective: To examine the relationship between three-dimensional mandibular morphology and growth hormone receptor (GHR) gene variants in a healthy Japanese population., Materials and Methods: The subjects, who were unrelated Japanese orthodontic patients, consisted of 64 men and 114 women. Using the Taqman genotyping assay, GHR gene rs6184 and rs6180 variants were detected in genomic DNA extracted from saliva. Mandibular volume and length were measured from cone-beam computed tomography images that were analyzed using Analyze image-processing software. The relationship between GHR gene variants and three-dimensional mandibular morphology was statistically examined., Results: Statistical significance for the relationship between the distance between the left and right coronoid processes and rs6180 was noted (P < .05)., Conclusion: Our results indicate that the GHR variant rs6180 is associated with the distance between the left and right coronoid process in the Japanese subjects.

Objective: To investigate the effects of condylar extracapsular injuries on the development of the mandibular condyle and try to find a way to treat condylar hyperplasia by electively using such injuries to restrict the overdeveloped mandibular condyle., Study Design: Sixty 6-month-old beagle puppies were divided randomly into five groups: blank control; unilateral fracture to the condylar neck; unilateral fracture to the condylar neck treated with rigid internal fixation; unilateral periosteum injury; unilateral decortication of the condylar neck. Computed tomography, 99 m Tc single-photon emission computed tomography, and tetracycline-calcein double-labeling were performed after surgery. The puppies were sacrificed 12 and 24 weeks after surgery. Morphologic analyses and examination of growth activity were done., Results: Unilateral fracture of the condylar neck without fixation caused local morphologic changes during the early postoperative period, but compensatory growth of the condyle altered such changes after healing. The other types of injury failed to inhibit the growth of the condyle and the mandible, whereas functional deviation of the chin was found after unilateral fracture of the condylar neck with or without fixation., Conclusions: The four types of extracapsular injury described here failed to inhibit the growth of the mandibular condyle and could not be selected as alternatives to treat condylar hyperplasia., (Copyright © 2016 Elsevier Inc. All rights reserved.)

The role of myosin light chain II (MLC‑II) in cellular differentiation of rat mandibular condylar chondrocytes (MCCs) induced by cyclical uniaxial compressive stress (CUCS) remains unclear. In the current study, a four‑point bending system was used to apply CUCS to primary cultured MCCs from rats. It was identified that CUCS stimulated features of cellular differentiation including morphological alterations, cytoskeleton rearrangement and overproduction of proteoglycans. Furthermore, CUCS promoted runt‑related transcription factor‑2 (RUNX2) expression at mRNA (P<0.01) and protein levels (P<0.05) and elevated alkaline phosphatase (ALP) activity (P<0.01), which are both markers of osteogenic differentiation. Under conditions of stress, western blotting indicated that the ratio of phosphorylated MLC‑II to total MLC‑II was increased significantly (P<0.05). Silencing MLC‑II by RNA interference reduced ALP activity (P<0.01), and eliminated RUNX2 mRNA expression (P<0.01). Addition of the MLC kinase inhibitor, ML‑7, reduced the CUCS‑associated upregulation of RUNX2 expression (P<0.01) and ALP activity (P<0.01). The data indicated that CUCS promoted cellular differentiation of rat primary MCCs, and this was suggested to be via the phosphorylation of MLC‑II.

Aim: The reported effects of Bionator treatment in patients with mandibular retrognathism are conflicting. This study evaluated the changes in craniofacial morphology resulting from treatment with a Bionator, based on measurement percentiles previously reported, to clarify the mechanism of the effect of this commonly used functional device., Materials and Methods: Study Design: Retrospective., Setting: A private orthodontic clinic., Participants: Forty-two children (mean age, 10.13 years) requiring treatment with a Bionator for Class II malocclusion (mandibular retrognathism). Children were randomly assigned to a Bionator group with or without an expansion screw. Measurements on lateral cephalometric radiographs were taken before and upon completion of Bionator treatment. All parameters measured were characterised according to the measurement percentiles previously reported. Each parameter was compared before and after treatment for all patients and for each treatment group using Wilcoxon's test., Results: No significant differences in cranial length or mandibular body length were seen in any of the 3 groups, but anterior cranial base length and maxillary length were significantly decreased while mandibular ramus height and mandibular length were significantly increased after treatment in the Bionator with expansion screw group and in the all-patient group., Conclusions: The findings suggest that treatment with a Bionator with expansion screw during the growth and development stage results in increased mandible length and ramus height and inhibits the growth of the maxilla and anterior cranial base bone.

Activating FGFR3 mutations in human result in achondroplasia (ACH), the most frequent form of dwarfism, where cartilages are severely disturbed causing long bones, cranial base and vertebrae defects. Because mandibular development and growth rely on cartilages that guide or directly participate to the ossification process, we investigated the impact of FGFR3 mutations on mandibular shape, size and position. By using CT scan imaging of ACH children and by analyzing Fgfr3 Y367C/+ mice, a model of ACH, we show that FGFR3 gain-of-function mutations lead to structural anomalies of primary (Meckel's) and secondary (condylar) cartilages of the mandible, resulting in mandibular hypoplasia and dysmorphogenesis. These defects are likely related to a defective chondrocyte proliferation and differentiation and pan-FGFR tyrosine kinase inhibitor NVP-BGJ398 corrects Meckel's and condylar cartilages defects ex vivo. Moreover, we show that low dose of NVP-BGJ398 improves in vivo condyle growth and corrects dysmorphologies in Fgfr3 Y367C/+ mice, suggesting that postnatal treatment with NVP-BGJ398 mice might offer a new therapeutic strategy to improve mandible anomalies in ACH and others FGFR3-related disorders., (© The Author 2016. Published by Oxford University Press.)

Objective: To assess the effects of two phase treatment(Herbst and fixed appliance) and fixed appliance treatment only(edgewise appliance) on temporomandibular joint in Cass Ⅱ patients with mandibular retrusion using cone-beam CT(CBCT) analysis., Methods: Thirty Class Ⅱ patients with mandibular retrusion in the permanent dentition were divided into two groups. Group A consisted of 15 patients with two phase treatment. Group B consisted of 15 patients with fixed appliance treatment only. CBCT was taken before(T1) and after(T2) treatment. The Invivo Dental software was used to calculate the relevant parameters of temporomandibular joint. Wilcoxon analysis was carried out., Results: In group A, the condylar anterior-posterior diameters(7.41[2.55]) and the condylar head height(3.58[0.86]) increased significantly after treatment(P<0.05). In group B, all skeletal measurements had no significant changes(P> 0.05) after treatment. The changes of condylar head height in group A(0.60[0.48]) showed greater than in group B(0.02[0.21]) (P<0.05). No significant differences in the temporomandibular joint spaces were found before and after treatment, and between the two groups(P>0.05)., Conclusions: Compared with fixed appliance treatment only, except for condylar growth changes, no significant changes of other skeletal morphology of the temporomandibular joint and the condyle position within the glenoid fossa were found between patients with two phase treatment and with fixed appliance treatment only.

Anterior disc displacement is a common subtype seen in temporomandibular disorders (TMD) patients. It may cause mandibular movement disorders, such as clicking of joint, intermittent closed lock, limitation of mouth opening, etc. These disorders may affect the life qualities of patients. Anterior disc displacement may also cause mandibular malformations, especially among adolescents, which may affect the growth of condyle, therefore may have a correlation with mandibular retrusion or mandibular deviation when grown up. This paper going to review the influences of anterior disc displacement on oral mandibular function and morphology and their biological mechanisms.

Objective: To examine the effects of imbalance of masticatory muscle activity of the rat mandible on the condylar cartilage and subchondral bone during the growth period., Design: Forty 5-week-old male Wistar rats were randomly divided into experimental (n=20) and control (n=20) groups. In the experimental group, the left masseter muscles were resected. The rats were sacrificed at 7 or 9 weeks of age in both groups. Microcomputed tomography was used to determine the three-dimensional morphology and cancellous bone structure. For histological and histochemical examination, 5-μm-thick serial frontal sections of the condyle were stained with toluidine blue and immunostained with asporin and TGF-β1 to evaluate the promotion and inhibition of chondrogenesis., Results: In the experimental group, microcomputed tomography analysis showed asymmetric growth; the resected side condyles showed degenerative changes. Histological analysis showed that the total cartilage in the central region of the resected side was significantly thinner than in the non-resected side in the experimental group, as well as in the control group. Compared with the control group, the expression of asporin was significantly higher in the resected side, and significantly lower in the non-resected side. In contrast, the expression of TGF-β1-immunopositive cells in the non-resected side was significantly higher than in the resected side and the control group., Conclusions: These findings imply that lateral imbalance of masseter muscle activity lead to inhibition of chondrogenesis and induce asymmetric formation of the condyle during the growth period., (Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.)

This study examined the effects of a bite-jumping appliance combined with low-intensity pulsed ultrasound (LIPUS) stimulation on the mandibular condyle of growing rats using micro CT (mCT) and histological examinations. Twelve Wistar rats were divided into three groups of four individuals each: Group 1 was an untreated control group, Group 2 received bite-jumping appliances, and Group 3 received bite-jumping appliances and LIPUS stimulation (15 min/day, 2 weeks) to the temporomandibular region. We measured the length and three-dimensional bone volume of each rat's mandibular condyle using mCT. The condylar cartilage was observed after the rats had been sacrificed. There was no significant difference in condylar sagittal width among the groups. The bite-jumping appliance combined with LIPUS stimulation increased the condylar major axis, mandibular sagittal length and condylar bone volume to a greater degree than use of the bite-jumping appliance alone. Histological examination demonstrated hypertrophy of the condylar cartilage layers, the fibrous layer and hypertrophic cell layer of the rats treated with bite-jumping appliances combined with LIPUS stimulation in comparison to rats treated with bite-jumping appliances alone. (J Oral Sci 58, 415-422, 2016).

Objective: To investigate differentially expressed proteins in rat mandibular condylar cartilage (MCC) chondrocytes caused by initial mastication for short postnatal periods., Methods: Four groups of protein samples were extracted from primary cultured rat MCC chondrocytes, harvested from eigthy postnatal SD rats aged 1,7,14 and 28 days, with twenty in each group. Total proteins were labelled with isobaric tags for relative and absolute quantification (iTRAQ) reagents. Two-dimensional nano-high-performance liquid chromatography (HPLC) and matrix-assisted laser desorption ionization-time-of-flight/ time-of-flight (MALDI-TOF/TOF) mass spectrometry analysis with iTRAQ technique were performed. All data were analysed by MASCOT software with the SWISSPROT protein database. Furthermore, bioinformatics and statistical analysis were performed to classify their cellular components, biological processes, molecular functions and metabolic pathway by the PANTHER database., Results: In total, 137 differentially expressed proteins were identified during MCC growth and were assigned to one or more cellular components. According to the PANTHER analysis, a significant proportion of proteins are involved in the metabolic process, cellular process, biological regulation, developmental process and response to stimulus. The most extensive molecular function was 43% in catalytic activity. In addition, it was found that proteins in MCC chondrocytes change markedly on the growth stage of eruption of the teeth., Conclusion: This study provides an integrated perspective of molecular mechanisms regulating early normal postnatal growth and development of rat MCC at the protein level.

Introduction: Cervical vertebral maturation (CVM) methods have been criticized because of their subjective nature. The aims of this study were (1) to analyze the morphometric changes in the outline of the second to fourth cervical vertebrae with growth and (2) to test the validity of the CVM method for determining the mandibular growth peak., Methods: Lateral cephalograms of 25 participants from ages 10 to 16 years were acquired from the Burlington Growth Study, and the CVM stage was qualitatively determined. Mandibular and cervical vertebral semilandmarks were then digitized, and point distribution models were used to describe the morphometric templates of the vertebrae in relation to chronologic age and the timing of peak mandibular growth. Mixed model analysis was used to determine the relationship between mandibular length, sex, CVM stage, and chronologic age., Results: Morphometric changes of the second to fourth cervical vertebrae during growth were consistent with the CVM descriptions. However, mandibular length changes were not significantly associated with CVM stages after adjusting for chronologic age. Morphometric templates of vertebral shapes before and during the mandibular growth peak were similar, with changes detectable only after the growth peak had passed. Morphometric vertebral shape changes varied between the sexes., Conclusions: Morphometric changes of the cervical vertebrae and the CVM method could not accurately identify the mandibular growth peak., (Copyright © 2016 American Association of Orthodontists. Published by Elsevier Inc. All rights reserved.)

For decades, it has been widely accepted that hypertrophic chondrocytes undergo apoptosis prior to endochondral bone formation. However, very recent studies in long bone suggest that chondrocytes can directly transform into bone cells. Our initial in vivo characterization of condylar hypertrophic chondrocytes revealed modest numbers of apoptotic cells but high levels of antiapoptotic Bcl-2 expression, some dividing cells, and clear alkaline phosphatase activity (early bone marker). Ex vivo culture of newborn condylar cartilage on a chick chorioallantoic membrane showed that after 5 d the cells on the periphery of the explants had begun to express Col1 (bone marker). The cartilage-specific cell lineage-tracing approach in triple mice containing Rosa 26(tdTomato) (tracing marker), 2.3 Col1(GFP) (bone cell marker), and aggrecan Cre(ERT2) (onetime tamoxifen induced) or Col10-Cre (activated from E14.5 throughout adult stage) demonstrated the direct transformation of chondrocytes into bone cells in vivo. This transformation was initiated at the inferior portion of the condylar cartilage, in contrast to the initial ossification site in long bone, which is in the center. Quantitative data from the Col10-Cre compound mice showed that hypertrophic chondrocytes contributed to ~80% of bone cells in subchondral bone, ~70% in a somewhat more inferior region, and ~40% in the most inferior part of the condylar neck (n = 4, P < 0.01 for differences among regions). This multipronged approach clearly demonstrates that a majority of chondrocytes in the fibrocartilaginous condylar cartilage, similar to hyaline cartilage in long bones, directly transform into bone cells during endochondral bone formation. Moreover, ossification is initiated from the inferior portion of mandibular condylar cartilage with expansion in one direction., (© International & American Associations for Dental Research 2015.)

Aim: To investigate the effects of muscle denervation and the introduction of the β2-adrenoceptor agonist, formoterol, on the relationship between muscles and underlying skeletal growth., Method: Thirty-one (4-week-old) male Sprague-Dawley rats were assigned to four groups: Surgical Sham; Denervated; Denervated + β2-agonist; and β2-agonist only. The Surgical Sham group had the left masseteric nerve exposed but not sectioned. Both of the denervated groups had the left masseteric nerve exposed and sectioned. The groups receiving the β2-agonist had formoterol directly injected into the left masseter muscle every three days for eight weeks. Sixteen angular and linear skeletal measurements were assessed in the overall craniofacial region and the mandible via standardised digital radiography in three views: lateral head, submento-vertex and right and left disarticulated hemi-mandibles., Results: The findings indicated that, following surgical denervation of the masseter muscle, there were significant changes in the muscle and in the subsequent development of the underlying skeletal structures. The post-surgical changes were largely offset by the administration of a β2-agonist, formoterol, which attenuated muscle atrophy. However, the administration of the β2-agonist only, without surgical denervation, did not lead to changes in skeletal facial form., Conclusions: Denervation atrophy of the masseter muscle results in statistically significant changes in the development of the underlying skeleton. The changes, however, are localised to areas of muscle attachment. The administration of the β2-agonist, formoterol, despite its effect on muscle anabolism, does not have a significant effect on underlying skeletal growth.

The temporomandibular joint (TMJ) of growing rats fed a soft diet is reported to be smaller in size and to have thinner condyle and glenoid fossa cartilage than rats fed a solid diet. The aim of this study was to determine the effect of a soft diet on the collagens and chondrocytes in the growing TMJ cartilage. Forty-eight male Wistar rats were divided into a control group fed a solid diet and an experimental group fed a liquid diet for 1-8 weeks. After the experimental period, the TMJs were harvested and examined histologically, immunohistochemically for collagen types I, II, and X, and with transmission electron microscopy. The condylar cartilage in the experimental rats showed weak immunoreactions for three types of collagens compared with the controls. The ultrastructure had fewer fine collagen fibrils in the experimental rats compared with that of the controls. The glenoid fossa cartilage in the experimental rats showed narrower Alcian blue-positive areas than the control staining. The immunoreactions for three types of collagen in the experimental rats were also weaker than those of the controls. The chondrocytes in the experimental rats appeared dark, had extended thin cytoplasmic processes, and had formed gap junctions, as assessed by transmission electron microscopy. Fewer fine collagen fibrils, but thick bands of collagen fibrils were observed in the glenoid fossa of the experimental cartilage. The results of the present study showed that a liquid diet had deleterious effects on the quality and quantity of collagens and chondrocytes in the TMJ cartilage in growing rats., (Copyright © 2015. Published by Elsevier GmbH.)