The effects of dietary loading on the transdifferentiation of condylar chondrocytes.

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-CreERT2 (AcanLineage); R26RTdTomato; 2.3 Col10a1-GFP and twelve 3-week-old male Col10a1-Cre (Col10a1Lineage); R26RTdTomato; 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 AcanLineage 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 AcanLineage-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-AcanLineage-derived bone cells was not significantly different among groups (P = 0.938). Col10a1Lineage mice showed the same trend. CONCLUSIONS: Dietary loading directly affects condyle chondrogenesis and chondrocyte transdifferentiation, which alters the extent of condylar growth and remodeling.

ADAMTS5 is required for normal trabeculated bone development in the mandibular condyle.

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, (Adamts5tm1Dgen/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.

Mandibular ramus height and condyle distance asymmetries in individuals with different facial growth patterns: a cone-beam computed tomography study.

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.

Effects of occlusion modification on the remodelling of degenerative mandibular condylar processes.

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-1ß. 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.

Relationship between mandibular condyle and articular eminence cortication with mandibular cortical index on cone-beam CT.

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.

Meckel's and condylar cartilages anomalies in achondroplasia result in defective development and growth of the mandible.

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 Fgfr3Y367C/+ 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 Fgfr3Y367C/+ 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.

Effect of different masticatory functional demands on the 3D mandibular condyle morphology of growing rats using posterior bite-blocks.

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.

Effect of Rapid Maxillary Expansion on Condyle-fossa Relationship in Growing Patients.

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.

Mandibular Condylar Aplasia Treated with a Functional Appliance: A Five years Follow Up.

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.

Estrogen receptor alpha mediates mandibular condylar cartilage growth in male mice.

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.

Morphometric analysis of cervical vertebrae in relation to mandibular growth.

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.

Clarifying the mechanism of effect of the Bionator for treatment of maxillary protrusion: A percentile growth study.

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.

A correlational study of serum alkaline phosphatase level and developmental mandibular laterognathism.

The abnormal cartilage/bone metabolism in unilateral condyle may be a direct factor that contributes to developmental mandibular laterognathism. However, although many molecules have been demonstrated to play crucial roles in the development of temporomandibular joints, the exact molecular mechanisms that lead to the disrupted condylar cartilage/bone development were greatly unknown. In this retrospective study, our findings revealed that serum alkaline phosphatase (ALP) level in adult patients with developmental mandibular laterognathism was lower than that in control subjects, and the serum ALP levels continue to reduce in adult patients (>20 years old). Although the exact relationship between the lower serum ALP level and developmental mandibular laterognathism is unclear, the findings further support the opinion that the condylar growth may sustain for a long time in the affected condyle in patients with developmental mandibular laterognathism and offer an alternative choice to use total serum ALP activity as a possible biomarker to assess condylar growth activity in patients with developmental mandibular laterognathism.

Changes in the location of the human mandibular foramen as a function of growth and vertical facial type.

OBJECTIVE: A previous cross-sectional investigation showed that the mandibular foramen location depends on the age and the vertical facial pattern of growing individuals. The aim of the present longitudinal study was to explain how these factors influence the distance between the foramen and the occlusal plane. It is known that a certain distance is necessary for a successful inferior alveolar nerve block in clinical dentistry. MATERIALS AND METHODS: This distance, as well as another four cephalometric variables, were measured on both pre-treatment and 10-year post-treatment lateral cephalometric radiographs collected from 50 patients who underwent orthodontic treatment. The changes between these two sets of measurements were also calculated. RESULTS: A multiple regression analysis was performed using the pre-treatment age, the pre-treatment inter-maxillary angle, the rotation of the occlusal plane and the change in mandibular ramus height as independent variables and the change of foramen-occlusal plane distance as a dependent variable. The independent variables under investigation were found to account for more than half of the variability of the foramen-occlusal plane distance (r = 0.732; p < 0.001). CONCLUSION: In very young individuals the mandibular foramen is located approximately at the level of the occlusal plane. With age it moves upwards relative to the occlusal plane and more so for those individuals with a low anterior facial height (short-face vertical facial type). These observations are, at least, partially explained by the differential growth of the various elements of the maxillo-mandibular complex and the change of the inclination of the occlusal plane.

Impact of local steroid or statin treatment of experimental temporomandibular joint arthritis on bone growth in young rats.

INTRODUCTION: Juvenile idiopathic arthritis in temporomandibular joints (TMJs) is often treated with intra-articular steroid injections, which can inhibit condylar growth. The purpose of this study was to compare simvastatin (a cholesterol-lowering drug that reduces TMJ inflammation) with the steroid triamcinolone hexacetonide in experimental TMJ arthritis. METHODS: Joint inflammation was induced by injecting complete Freund's adjuvant (CFA) into the TMJs of 40 growing Sprague Dawley rats; 4 other rats were left untreated. In the same intra-articular injection, one of the following was applied: (1) 0.5 mg of simvastatin in ethanol carrier, (2) ethanol carrier alone, (3) 0.15 mg of triamcinolone hexacetonide, (4) 0.5 mg of simvastatin and 0.15 mg of triamcinolone hexacetonide, or (5) nothing additional to the CFA. The animals were killed 28 days later, and their mandibles were evaluated morphometrically and with microcomputed tomography. RESULTS: The analysis showed that the TMJs subjected to CFA alone had decreased ramus height compared with those with no treatment (P <0.05). Groups that had injections containing the steroid overall had decreases in weight, ramus height, and bone surface density when compared with the CFA-alone group (P <0.0001). Groups that had injections containing simvastatin, however, had overall increases in weight (P <0.0001), ramus height (P <0.0001), condylar width (P <0.05), condylar bone surface density (P <0.05), and bone volume (P <0.0001) compared with the groups receiving the steroid injections, and they were not different from the healthy (no treatment) group. CONCLUSIONS: Treatment of experimentally induced arthritis in TMJs with intra-articular simvastatin preserved normal condylar bone growth.

Effect of chin-cup treatment on the temporomandibular joint: a systematic review.

AIM: To systematically search the literature and assess the available evidence for the influence of chin-cup therapy on the temporomandibular joint regarding morphological adaptations and appearance of temporomandibular disorders (TMD). MATERIALS AND METHODS: Electronic database searches of published and unpublished literature were performed. The following electronic databases with no language and publication date restrictions were searched: MEDLINE (via Ovid and PubMed), EMBASE (via Ovid), the Cochrane Oral Health Group's Trials Register, and CENTRAL. Unpublished literature was searched on ClinicalTrials.gov, the National Research Register, and Pro-Quest Dissertation Abstracts and Thesis database. The reference lists of all eligible studies were checked for additional studies. Two review authors performed data extraction independently and in duplicate using data collection forms. Disagreements were resolved by discussion or the involvement of an arbiter. RESULTS: From the 209 articles identified, 55 papers were considered eligible for inclusion in the review. Following the full text reading stage, 12 studies qualified for the final review analysis. No randomized clinical trial was identified. Eight of the included studies were of prospective and four of retrospective design. All studies were assessed for their quality and graded eventually from low to medium level of evidence. Based on the reported evidence, chin-cup therapy affects the condylar growth pattern, even though two studies reported no significance changes in disc position and arthrosis configuration. Concerning the incidence of TMD, it can be concluded from the available evidence that chin-cup therapy constitutes no risk factor for TMD. CONCLUSION: Based on the available evidence, chin-cup therapy for Class III orthodontic anomaly seems to induce craniofacial adaptations. Nevertheless, there are insufficient or low-quality data in the orthodontic literature to allow the formulation of clear statements regarding the influence of chin-cup treatment on the temporomandibular joint.

Effects of a liquid diet on the temporomandibular joint of growing rats.

OBJECTIVE: The aim of the present study was to clarify the effects of a liquid diet on the temporomandibular joint (TMJ) in growing rats. MATERIALS AND METHODS: Twenty-four male Wistar rats were weaned at 21 days and divided into control and experimental groups (12 in each group). Control rats were fed a solid diet and experimental rats were fed a liquid diet from 1 to 8 weeks. After injection with 5-bromo-2'-deoxyuridine (BrdU), the animals were perfused and the heads were removed. Serial coronal sections of the TMJ were stained with hematoxylin and eosin, or BrdU immunohistochemistry was done (12 rats in each group). Three dimensions and the thicknesses of the cartilage layers of the TMJ were measured, and cell proliferation in the TMJ was examined. RESULTS: After 4 weeks, the height and width of the mandibular fossa and the width and length of the mandibular condyle were smaller in the experimental groups than in the control groups. The cartilage layer in these areas was also thinner at 4 weeks. The BrdU levels in the intermediate zone of the mandibular fossa (at 4 weeks) and the mandibular condyle (at 1 and 4 weeks) were lower in the experimental groups than in the controls. CONCLUSION: These findings suggest that the growth of the mandibular fossa and mandibular condyle of rats was inhibited by the low proliferative activity of intermediate zone cells induced by liquid feeding.

Skeletal effects of the alteration of masseter muscle function.

AIM: To investigate the effects of muscle denervation and the introduction of the ß2-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 + ß2-agonist; and ß2-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 ß2-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 ß2-agonist, formoterol, which attenuated muscle atrophy. However, the administration of the ß2-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 ß2-agonist, formoterol, despite its effect on muscle anabolism, does not have a significant effect on underlying skeletal growth.

Estrogen via estrogen receptor beta partially inhibits mandibular condylar cartilage growth.

OBJECTIVE: Temporomandibular joint (TMJ) diseases predominantly afflict women, suggesting a role for female hormones in the disease process. However, little is known about the role of estrogen receptor (ER) signaling in regulating mandibular condylar cartilage growth. Therefore, the goal of this study was to examine the effects of altered estrogen levels on the mandibular condylar cartilage in wild type (WT) and ER beta Knockout (KO) mice. MATERIALS AND METHODS: 21-day-old female WT (n = 37) and ER beta KO mice (n = 36) were either sham operated or ovariectomized, and treated with either placebo or estradiol. The mandibular condylar cartilage was evaluated by histomorphometry, proliferation was analyzed by double ethynyl-2'-deoxyuridine/bromodeoxyuridine (EdU/BrdU) labeling, and assays on gene and protein expression of chondrocyte maturation markers were performed. RESULTS: In WT mice, ovariectomy caused a significant increase in mandibular condylar cartilage cell numbers, a significant increase in Sox9 expression and a significant increase in proliferation compared with sham operated WT mice. In contrast, ovariectomy did not cause any of these effects in the ER beta KO mice. Estrogen replacement treatment in ovariectomized WT mice caused a significant decrease in ER alpha expression and a significant increase in Sost expression compared with ovariectomized mice treated with placebo. Estrogen replacement treatment in ovariectomized ER beta KO mice caused a significant increase in Col2 expression, no change in ER alpha expression, and a significant increase in Sost expression. CONCLUSION: Estrogen via ER beta inhibits proliferation and ER alpha expression while estrogen independent of ER beta induces Col2 and Sost expression.

Morphometric growth relationships of the immature human mandible and tongue.

The masticatory apparatus is a highly adaptive musculoskeletal complex comprising several relatively independent structural components, which assist in functions including feeding and breathing. We hypothesized that the tongue is elemental in the maintenance of normal ontogeny of the mandible and in its post-natal growth and development, and tested this using a morphometric approach. We assessed tongue and mandibular measurements in 174 (97 male) human cadavers. Landmark lingual and mandibular data were gathered individuals aged between 20 gestational weeks and 3 yr postnatal. In this analysis, geometric morphometrics assisted in visualizing the morphometrical growth changes in the mandible and tongue. A linear correlation in conjunction with principal component analysis further visualized the growth relationship between these structures. We found that the growth of the tongue and mandible were intrinsically linked in size and shape between 20 gestational weeks and 24 months postnatal. However, the mandible continued to change in shape and size into the 3rd yr of life, whereas the tongue only increased in size over this same period of time. These findings provide valuable insights into the allometric growth relationship between these structures, potentially assisting the clinician in predicting the behaviour of these structures in the assessment of malocclusions.