Formation of functional skeletal tissues requires highly organized steps of mesenchymal progenitor cell differentiation. The dental follicle (DF) surrounding the developing tooth harbors mesenchymal progenitor cells for various differentiated cells constituting the tooth root–bone interface and coordinates tooth eruption in a manner dependent on signaling by parathyroid hormone-related peptide (PTHrP) and the PTH/PTHrP receptor (PPR). However, the identity of mesenchymal progenitor cells in the DF and how they are regulated by PTHrP-PPR signaling remain unknown. Here, we show that the PTHrP-PPR autocrine signal maintains physiological cell fates of DF mesenchymal progenitor cells to establish the functional periodontal attachment apparatus and orchestrates tooth eruption. A single-cell RNA-seq analysis revealed cellular heterogeneity of PTHrP+ cells, wherein PTHrP+ DF subpopulations abundantly express PPR. Cell lineage analysis using tamoxifen-inducible PTHrP-creER mice revealed that PTHrP+ DF cells differentiate into cementoblasts on the acellular cementum, periodontal ligament cells, and alveolar cryptal bone osteoblasts during tooth root formation. PPR deficiency induced a cell fate shift of PTHrP+ DF mesenchymal progenitor cells to nonphysiological cementoblast-like cells precociously forming the cellular cementum on the root surface associated with up-regulation of Mef2c and matrix proteins, resulting in loss of the proper periodontal attachment apparatus and primary failure of tooth eruption, closely resembling human genetic conditions caused by PPR mutations. These findings reveal a unique mechanism whereby proper cell fates of mesenchymal progenitor cells are tightly maintained by an autocrine system mediated by PTHrP-PPR signaling to achieve functional formation of skeletal tissues.

Objective To assess 3D morphological variations and local and systemic biomarker profiles in subjects with a diagnosis of temporomandibular joint osteoarthritis (TMJ OA). Design Twenty-eight patients with long-term TMJ OA (39.9 ± 16 years), 12 patients at initial diagnosis of OA (47.4 ± 16.1 years), and 12 healthy controls (41.8 ± 12.2 years) were recruited. All patients were female and had cone beam CT scans taken. TMJ arthrocentesis and venipuncture were performed on 12 OA and 12 age-matched healthy controls. Serum and synovial fluid levels of 50 biomarkers of arthritic inflammation were quantified by protein microarrays. Shape Analysis MANCOVA tested statistical correlations between biomarker levels and variations in condylar morphology. Results Compared with healthy controls, the OA average condyle was significantly smaller in all dimensions except its anterior surface, with areas indicative of bone resorption along the articular surface, particularly in the lateral pole. Synovial fluid levels of ANG, GDF15, TIMP-1, CXCL16, MMP-3 and MMP-7 were significantly correlated with bone apposition of the condylar anterior surface. Serum levels of ENA-78, MMP-3, PAI-1, VE-Cadherin, VEGF, GM-CSF, TGFβb1, IFNγg, TNFαa, IL-1αa, and IL-6 were significantly correlated with flattening of the lateral pole. Expression levels of ANG were significantly correlated with the articular morphology in healthy controls. Conclusions Bone resorption at the articular surface, particularly at the lateral pole was statistically significant at initial diagnosis of TMJ OA. Synovial fluid levels of ANG, GDF15, TIMP-1, CXCL16, MMP-3 and MMP-7 were correlated with bone apposition. Serum levels of ENA-78, MMP-3, PAI-1, VE-Cadherin, VEGF, GM-CSF, TGFβ1, IFNγ, TNFα, IL-1α, and IL-6 were correlated with bone resorption.

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Introduction Conventional treatment for young Class III patients involves extraoral devices designed to either protract the maxilla or restrain mandibular growth. The use of skeletal anchorage offers a promising alternative to obtain orthopedic results with fewer dental compensations. Our aim was to evaluate 3-dimensional changes in the mandibles and the glenoid fossae of Class III patients treated with bone-anchored maxillary protraction. Methods Twenty-five consecutive skeletal Class III patients between the ages of 9 and 13 years (mean age, 11.10 ± 1.1 year) were treated with Class III intermaxillary elastics and bilateral miniplates (2 in the infrazygomatic crests of the maxilla and 2 in the anterior mandible). The patients had cone-beam computed tomography images taken before initial loading and at the end of active treatment. Three-dimensional models were generated from these images, registered on the anterior cranial base, and analyzed by using color maps. Results Posterior displacement of the mandible at the end of treatment was observed in all subjects (posterior ramus: mean, 2.74 ± 1.36 mm; condyles: mean, 2.07 ± 1.16 mm; chin: mean, −0.13 ± 2.89 mm). Remodeling of the glenoid fossa at the anterior eminence (mean, 1.38 ± 1.03 mm) and bone resorption at the posterior wall (mean, −1.34 ± 0.6 mm) were observed in most patients. Conclusions This new treatment approach offers a promising alternative to restrain mandibular growth for Class III patients with a component of mandibular prognathism or to compensate for maxillary deficiency in patients with hypoplasia of the midface. Future studies with long-term follow-up and comparisons with facemask and chincup therapies are needed to better understand the treatment effects.

Introduction The aims of this study were to analyze 3-dimensional skeletal changes in subjects with Class II malocclusion treated with the Herbst appliance and to compare these changes with treated Class II controls using 3-dimensional superimposition techniques. Methods Seven consecutive Herbst patients and 7 Class II controls treated with Class II elastics who met the inclusion criteria had cone-beam computed tomographs taken before treatment, and either after Herbst removal or at posttreatment for the control subjects. Three-dimensional models were generated from the cone-beam computed tomography images, registered on the anterior cranial bases, and analyzed using color maps and point-to-point measurements. Results The Herbst patients demonstrated anterior translation of the glenoid fossae and condyles (right anterior fossa, 1.69 ± 0.62 mm; left anterior fossa, 1.43 ± 0.71 mm; right anterior condyle, 1.20 ± 0.41 mm; left anterior condyle, 1.29 ± 0.57 mm), whereas posterior displacement predominated in the controls (right anterior fossa, −1.51 ± 0.68 mm; left anterior fossa, −1.31 ± 0.61 mm; right anterior condyle, −1.20 ± 0.41 mm; left anterior condyle, −1.29 ± 0.57 mm; P <0.001). There was more anterior projection of B-point in the Herbst patients (2.62 ± 1.08 mm vs 1.49 ± 0.79 mm; P <0.05). Anterior displacement of A-point was more predominant in the controls when compared with the Herbst patients (1.20 ± 0.53 mm vs −1.22 ± 0.43 mm; P <0.001). Conclusions Class II patients treated with the Herbst appliance demonstrated anterior displacement of the condyles and glenoid fossae along with maxillary restraint when compared with the treated Class II controls; this might result in more anterior mandibular projection.

Introduction the aim of this study was to evaluate the differences between 2 regions of maxillary voxel-based registration and to test the reproducibility of the registration. Methods 3D models were built for before treatment (T1) and after treatment (T2) Cone Beam CTs for 16 growing subjects. Landmarks were labeled in all T2 models of the maxilla, and voxel-based registration was performed independently by two observers, at two different times, using two different reference regions: 1) the Maxilla region (MAX) included the maxillary bone clipped inferiorly at the dentoalveolar processes, superiorly at the plane passing through the right and left orbitale points, laterally at the zygomatic processes through the orbitale point, and posteriorly at a plane passing through the distal surface of the second molars. 2) the Palate and Infra-zygomatic region (PIZ) had different posterior and anterior limits (at the plane passing through the distal of the first molar and distal of the canines, respectively). The differences between the registration regions were measured by comparing the distances between corresponding landmarks in the T2 registered models and comparing corresponding x,y,z coordinates from corresponding landmarks. Statistical analysis of the differences between T2 surface models was performed by evaluating the means and standard deviations of the distances between landmarks and by testing the agreement between coordinates from corresponding landmarks (ICC and Bland-Altman method). Results The means of the differences between landmarks from PIZ to MAX 3D T2 surface models for all of the regions of reference, times of registrations and observers combinations were smaller than 0.5 mm. The ICC and the Bland-Altman plots indicated adequate concordance. Conclusions Both regions of regional maxillary registration (MAX and PIZ) showed similar results and adequate intra- and inter-observer reproducibility.

The findings of this study demonstrate a comprehensive phenotypic characterization of TMJ health and disease at clinical, imaging and biological levels, using novel flexible and versatile open-source tools for a web-based system that provides advanced shape statistical analysis and a neural network based classification of temporomandibular joint osteoarthritis.

BackgroundThe objectives of this study were to develop and validate a novel analysis protocol to measure linear and angular measurements of tip and torque of each tooth in the dental arches of virtual study models.MethodsMaxillary and mandibular dental casts of 25 subjects with a full permanent dentition were scanned using a three-dimensional model scanner. Sixty points per arch were digitized on each model, five points on each tooth. A custom analysis to measure linear distances and angles of tip and torque was developed using a new reference plane passing as a best-fit among all of the lingual gingival points, with the intermolar lingual distance set as the reference X-axis. The linear distances measured included buccal, lingual, and centroid transverse widths at the level of canines, premolars, and molars as well as arch depth and arch perimeter.ResultsThere was no systematic error associated with the methodology used. Intraclass correlation coefficient values were higher than 0.70 on every measure. The average random error in the maxilla was 1.5° ± 0.4° for torque, 1.8° ± 0.5° for tip, and 0.4 ± 0.2 mm for linear measurements. The average random error in the mandible was 1.2° ± 0.3° for torque, 2.0° ± 0.8° for tip, and 0.1 ± 0.1 mm for the linear measurements.ConclusionsA custom digital analysis protocol to measure traditional linear measurements as well as tip and torque angulation on virtual dental casts was presented. This validation study demonstrated that the digital analysis used in this study has adequate reproducibility, providing additional information and more accurate intra-arch measurements for clinical diagnosis and dentofacial research.