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Objective: To investigate condylar bone density (BD) in children with craniofacial microsomia (CFM) and identify factors that contribute to early stage condylar resorption (CR) after mandibular distraction osteogenesis (MDO). Design: Retrospective study. Setting: Craniofacial department of a plastic surgery hospital. Patients: Fifty-one children with CFM classified as Pruzansky IIa based on complete pre-(T0) and post-MDO (T1) computed tomography (CT) data. Intervention and Main outcome measurements: Mimic 21.0 (Materialise Inc., Belgium) was used to measure bilateral BD and condylar height (CH) and volume (CV) of affected side. Children were split into groups based on either affected side BD or the distraction length (DL,25 mm as cutoff).Bilateral BD was compared using a paired t-test in each group. The CH and CV of affected side at T0 and T1 were compared. The relative values of the CH and CV (CH ratio) and the volume (CV ratio) of the affected side were compared across the groups. Results: The BD was lower on affected side than on unaffected side. Regarding BD, CH and CV decreased after MDO in group I, while the CH ratio and CV ratio of group I was lower than that of groups II and III. Regarding DL, the CV ratio was lower in Group L than Group S. Conclusions: The condylar bone quality on affected side is compromised in type IIa CFM. A low BD in combination with a larger distraction distance may increase the risk of CR; therefore, MDO in patients with such characteristics should be postponed. [ABSTRACT FROM AUTHOR]

The mandibular condylar cartilage (MCC) is an essential component of the temporomandibular joint, which orchestrates the vertical growth of the mandibular ramus through endochondral ossification with distinctive modes of cell differentiation. Parathyroid hormone–related protein (PTHrP) is a master regulator of chondrogenesis; in the long bone epiphyseal growth plate, PTHrP expressed by resting zone chondrocytes promotes chondrocyte proliferation in the adjacent layer. However, how PTHrP regulates chondrogenesis in the MCC remains largely unclear. In this study, we used a Pthrp-mCherry knock-in reporter strain to map the localization of PTHrP+ cells in the MCC and define the function of PTHrP in the growing mandibular condyle. In the postnatal MCC of Pthrp mCherry/+ mice, PTHrP-mCherry was specifically expressed by cells in the superficial layer immediately adjacent to RUNX2-expressing cells in the polymorphic layer. PTHrP ligands diffused across the polymorphic and chondrocyte layers where its cognate receptor PTH1R was abundantly expressed. We further analyzed the mandibular condyle of Pthrp mCherry/mCherry mice lacking functional PTHrP protein (PTHrP-KO). At embryonic day (E) 18.5, the condylar process and MCC were significantly truncated in the PTHrP-KO mandible, which was associated with a significant reduction in cell proliferation across the polymorphic layer and a loss of SOX9+ cells in the chondrocyte layers. The PTHrP-KO MCC showed a transient increase in the number of Col10a1+ hypertrophic chondrocytes at E15.5, followed by a significant loss of these cells at E18.5, indicating that superficial layer–derived PTHrP prevents premature chondrocyte exhaustion in the MCC. The expression of Runx2, but not Sp7, was significantly reduced in the polymorphic layer of the PTHrP-KO MCC. Therefore, PTHrP released from cells in the superficial layer directly acts on cells in the polymorphic layer to promote proliferation of chondrocyte precursor cells and prevent their premature differentiation by maintaining Runx2 expression, revealing a unique PTHrP gradient-directed mechanism that regulates MCC chondrogenesis. [ABSTRACT FROM AUTHOR]

A growing body of evidence emerging supported that ectodysplasin-A (EDA) signaling pathway contributed to craniofacial development. However, their expression in condyle has not been elucidated yet. This study investigated the expression patterns of EDA, EDA receptor (EDAR), and EDAR-associated death domain (EDARADD) in condyle of postnatal mice. Histological staining and micro–computed tomography (CT) scanning showed that as endochondral ossification proceeded, the thickness of chondrocyte layer decreased, and the volume of mandibular condyle increased. Osteoclasts remained active throughout the condylar development. Immunohistochemistry staining demonstrated that EDA was expressed in almost all layers during the first 2 weeks after birth. EDA shifted from the mature and hypertrophic layers to fibrous and proliferating layers at postnatal 3 weeks. As condyle matured, the distribution of EDA tended to be limited to hypertrophic layer. The distribution patterns of EDAR and EDARADD were consistent with EDA, while the level of EDAR expression was slightly lower. mRNA expression levels of EDA signaling pathway-related components increased after birth. Furthermore, we evaluated the expression of EDA using ATDC5 in vitro. EDA increased during the late stage of chondrogenesis. These findings proved that EDA signaling pathway was involved in condylar development and acted as a regulatory factor in condylar maturation and differentiation. [ABSTRACT FROM AUTHOR]

Rhabdomyosarcoma affects mainly pediatric patients and is currently classified into four categories: embryonal, alveolar, pleomorphic, and spindle cell/sclerosing. Recently, a molecular group of spindle cell/sclerosing rhabdomyosarcoma demonstrated new fusion transcripts involving FET -family genes with TFCP2. In this report, we describe a rare case of spindle cell/sclerosing rhabdomyosarcoma in a 19-year-old woman, presenting as a destructive lesion involving the condyle of mandible. Next generation sequencing was performed, revealing a FUS::TFCP2 fusion and deletion of ALK gene. Alectinib therapy was initiated, which resulted in a favorable response for 4 months. However, the patient died due progression of the tumor. To make an accurate diagnosis and ensure appropriate patient management, it is necessary to be aware of this variant and use proper immunohistochemical stains when facing malignant mesenchymal bone lesions, expanding its differential diagnosis. [ABSTRACT FROM AUTHOR]

A 74-year-old Japanese woman with a 1-year history of right preauricular pain and a 2-month history of bleeding from the right ear was admitted to our department. Tumor was observed in the anterior wall in the right external auditory canal. Bony swelling of the right preauricular area was palpated. Computed tomography revealed an ill-defined, osteogenic tumor around the mandibular condyle with a destructive bony lesion involving the temporal bone. Magnetic resonance imaging revealed a 2.0 × 1.5 × 1.3-cm solid tumor around the mandibular condyle, exhibiting a low-intensity signal on T1-weighted imaging and an isointense central area surrounded by low-signal intensity on T2-weighted imaging. Histological examination of biopsy specimens revealed diffuse-type tenosynovial giant cell tumor (D-TGCT). After the feeding arteries for the tumor were embolized, the patient underwent surgery with combined temporal craniotomy and mandibular condylectomy. The soft and cystic tumor with calcification located in the extradural space was totally resected along with the mandibular condyle. No facial paralysis or recurrence was evident as of 6 months postoperatively. To date, only 23 cases of D-TGCT arising in the temporomandibular joint (TMJ) with ear involvement have been reported since 2011. We report successful resection of a rare case of D-TGCT arising in the TMJ. [ABSTRACT FROM AUTHOR]

The position of a bone conduction (BC) transducer influences the perception of BC sound, but the relation between the stimulation position and BC sound perception is not entirely clear. In the current study, eleven participants with normal hearing were evaluated for their hearing thresholds and speech intelligibility for three stimulation positions (temple, mastoid, and condyle) and four types of ear canal occlusion produced by headphones. In addition, the sound quality for three types of music was rated with stimulation at the three positions. Stimulation at the condyle gave the best performance while the temple showed the worst performance for hearing thresholds, speech intelligibility, and sound quality. The in-ear headphones gave the highest occlusion effect while fully open headphones gave the least occlusion effect. BC stimulated speech intelligibility improved with greater occlusion, especially for the temple stimulation position. The results suggest that BC stimulation at the condyle is generally superior to the other positions tested in terms of sensitivity, clarity, and intelligibility, and that occlusion with ordinary headphones improves the BC signal. [ABSTRACT FROM AUTHOR]

Objective: Mandibular distraction osteogenesis (MDO) is frequently performed to address airway obstruction in patients with Pierre Robin sequence (PRS), though more recently the technique of orthodontic airway plating (OAP) has gained traction. We aimed to evaluate OAP compared to MDO for airway obstruction in PRS. Design: A systematic literature search across PubMed, Embase, and Google Scholar identified all studies published in English, which involved MDO or any form of OAP as treatments for PRS. All relevant articles were reviewed in detail and reported on, adhering to PRISMA guidelines. Main Outcome Measures: Airway (tracheostomy avoidance, decannulation rate), feeding (full oral feeding tolerance). Results: Literature search identified 970 articles, of which 42 MDO studies and 9 OAP studies met criteria for review. A total of 1159 individuals were treated with MDO, and 322 individuals were treated with OAP. Primary outcomes appear similar for MDO and OAP at face value; however, this must be interpreted with different pretreatment contexts in mind. Conclusions: Orthodontic airway plating may be considered for airway obstruction in PRS, as some airway-related and feeding-related outcomes appear similar with MDO, per existing evidence in the literature. However, since PRS severity differed between studies, OAP cannot be uniformly considered a replacement for MDO. Further research is required to more comprehensively assess these treatment modalities inclusive of metrics that allow for direct comparison. [ABSTRACT FROM AUTHOR]

Type H vessel is a specific vessel subtype that is strongly positive for CD31 and endomucin (CD31hiEmcnhi). It has already been identified that it can tightly regulate the coupling of angiogenesis and osteogenesis in the long bone of mice and human beings. The long bone is formed through endochondral ossification, which is the same type of process happening in mandibular condyle. Although the ossification of long bone and mandibular condyle has the same developmental process, the existence of type H vessels in the mouse condyle remains unclear. To address this, we identified that abundant type H vessels existed in the subchondral bone of the mouse condylar head and endosteum of the mouse condylar neck. Meanwhile, immunofluorescence imaging of the condyles in different ages of male C57BL/6J mice demonstrated that type H vessels decreased while aging. Furthermore, we validated a positive correlation between type H vessels and Osterix+ osteoprogenitors in the condyle induced by mandibular advancement. Mechanistically, we confirmed that deferoxamine mesylate, which promoted the proliferation of type H endothelial cells by activating hypoxia-inducible factor 1α (HIF-1α) signaling pathways, largely prevented the osteopenia in the condyle induced by botulinum toxin type A. Collectively, these results demonstrate that in the mouse condyle, type H vessels in areas of high function positively correlate with bone formation. In addition, we show a novel influence of HIF-1α signaling on osteogenesis via an increase in type H vessels. In conclusion, promoting angiogenesis of type H vessels is a promising strategy for the therapeutic improvement of osteogenesis in mandibular condyle. [ABSTRACT FROM AUTHOR]

Objective: To assess the symmetry of the mesiodistal angulations of maxillary and mandibular teeth in patients with unilateral cleft lip and palate (UCLP) and compare with the class I control group without cleft lip and palate (CLP). Design: A retrospective study. Setting: University department. Patients, Participants: The panoramic radiographs of 45 orthodontically untreated individuals with nonsyndromic UCLP (mean age 14.13 ± 0.75 years) and 45 skeletal class I individuals without CLP (mean age 14.01 ± 0.74 years). Interventions: The line passing through the most superior points of the condyles was taken as the reference. The angle between the long axes of the maxillary and mandibular teeth and reference line was measured digitally. With the purpose of determining condylar symmetry, mandibular asymmetry index measurements were utilized. Independent samples t test and paired samples t test were used for the statistical analyses. Main Outcome Measure(s): The mesiodistal angulation of the maxillary and mandibular teeth in patients with UCLP was measured. The differences between the contralateral sides were determined and compared to class I individuals without CLP. Results: No statistically significant difference was found among the condylar asymmetry in both groups (P >.05).The significant differences between the cleft and noncleft sides in the UCLP group was observed in the maxillary central, canine, first premolar and second molar teeth (P <.001, P =.002, P =.013, P =.012, respectively). The mean differences were found to be higher in the central and lateral incisors, canines and first premolars in the UCLP group (P <.001, P =.006, P =.001, respectively). Conclusions: Although the cleft-side maxillary central incisors tipped in a distal direction in patients with UCLP, the canine and first premolar showed more inclinations toward the mesial direction. [ABSTRACT FROM AUTHOR]

The article describes a case of an older female patient who was diagnosed with Jefferson burst fracture after falling on a staircase. Topics mentioned include the symptoms experienced by the patient, the use of computerized tomography to show lateral displacement and a tear of the transverse ligament, and a brief background of Collet-Sicard syndrome.

Introduction: Skeletal reconstruction in severe grades of hemifacial microsomia (HFM) continues to be challenging. Traditional techniques of autografts and osseous distraction for reconstruction of the glenoid fossa, condyle, and ramus can fall short of expectations and can create new problems. This intercontinental study analyzes the role of alloplastic skeletal rehabilitation in severe HFM. Methods: Ten consecutive patients with Pruzansky grade III HFM were reconstructed between October 2014 and July 2017 at 2 craniofacial centers following the same protocol. Data were gathered retrospectively from the medical records, including photographs and virtual planning records. Pre and postoperative photos were taken to compare occlusal status, interincisal opening, sagittal mandibular projection, and posterior facial height. Alloplastic reconstruction was accomplished using a custom designed titanium implant. Results: Ten consecutive skeletally mature patients with HFM with failed traditional reconstructions were successfully treated with virtually planned alloplastic reconstructions (11 joints) and simultaneous orthognathic surgery. The glenoid fossa, condyle, and ramus on the affected sides were reconstructed with custom designed titanium implants. All patients achieved occlusal stabilization, normalization of posterior facial height and sagittal mandibular projection, and maintenance or improved inter-incisal opening. There were no major complications or repeated surgeries. Follow-up ranges from 6 to 50 months. Conclusion: Alloplastic reconstruction allows for precise vertical reconstruction of the ramus and condyle and sagittal repositioning of the mandibular body. The glenoid fossa component is firmly anchored to the skull base assuring a stable centric relation on the reconstructed side. Consistent and acceptable results can be achieved in skeletally mature patients. [ABSTRACT FROM AUTHOR]

Temporomandibular joint (TMJ) osteoarthritis (TMJOA) disrupts extracellular matrix (ECM) homeostasis, leading to cartilage degradation. Upregulated a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)-5 leads to cleavage of its substrate aggrecan (Acan) and is considered a hallmark of TMJOA. However, most research on ADAMTS5-Acan turnover has focused on hyaline cartilage, not fibrocartilage, which comprises the TMJ. The mandibular condylar cartilage (MCC) of the TMJ is organized in zones, and chondrocytes are arranged in axial rows, yet the molecular mechanisms required to generate the MCC zonal architecture have not been elucidated. Here, we test the hypothesis that ADAMTS5 is required for development of the TMJ MCC. Adamts5+/+ and Adamts5-/- murine TMJs were harvested at postnatal day 7 (P7), P21, 2 mo, and 6 mo of age; histomorphometrics indicated increased ECM. Immunohistochemistry and Western blots demonstrated the expanded ECM correlated with increased Acan localization in Adamts5-/- compared to Adamts5+/+. Cell volume was also decreased in the MCC of Adamts5-/- due to both a reduction in cell size and less mature hypertrophic chondrocytes. Analysis of chondrogenic maturation markers by quantitative real-time polymerase chain reaction indicated Col2a1, Col10a1, and Sox9 were significantly reduced in Adamts5-/- MCC compared to that of Adamts5+/+. The older (6 mo) Adamts5-/- MCC exhibited changes in chondrogenic cell arrangements, including clustering and chondrogenic atrophy, that correlated with early stages of TMJOA using modified Mankin scoring. These data indicate a potentially novel and critical role of ADAMTS5 for maturation of hypertrophic chondrocytes and establishment of the zonal architecture that, when disrupted, may lead to early onset of TMJOA. [ABSTRACT FROM AUTHOR]

Craniofacial secondary cartilages of the mandibular condyle and temporomandibular joint (TMJ) eminence grow in response to the local mechanical environment. The intervening TMJ disc distributes normal loads over the cartilage surfaces and provides lubrication. A better understanding of the mechanical environment and its effects on growth, development, and degeneration of the TMJ may improve treatments aimed at modifying jaw growth and preventing or reversing degenerative joint disease (DJD). This review highlights data recorded in human subjects and from computer modeling that elucidate the role of mechanics in TMJ ontogeny. Presented data provide an approximation of the age-related changes in jaw-loading behaviors and TMJ contact mechanics. The cells of the mandibular condyle, eminence, and disc respond to the mechanical environment associated with behaviors and ultimately determine the TMJ components' mature morphologies and susceptibility to precocious development of DJD compared to postcranial joints. The TMJ disc may be especially prone to degenerative change due to its avascularity and steep oxygen and glucose gradients consequent to high cell density and rate of nutrient consumption, as well as low solute diffusivities. The combined effects of strain-related hypoxia and limited glucose concentrations dramatically affect synthesis of the extracellular matrix (ECM), which limit repair capabilities. Magnitude and frequency of jaw loading influence this localized in situ environment, including stem and fibrocartilage cell chemistry, as well as the rate of ECM mechanical fatigue. Key in vivo measurements to characterize the mechanical environment include the concentration of work input to articulating tissues, known as energy density, and the percentage of time that muscles are used to load the jaws out of a total recording time, known as duty factor. Combining these measurements into a mechanobehavioral score and linking these to results of computer models of strain-regulated biochemical events may elucidate the mechanisms responsible for growth, maintenance, and deterioration of TMJ tissues. [ABSTRACT FROM AUTHOR]

Objective: The purpose of the present study was to compare mandibular vertical asymmetry in patients with unilateral and bilateral cleft lip and palate and subjects with normal occlusion. Materials and Methods: Cone beam computed tomography scans of three groups consisting of 20 patients with unilateral cleft lip and palate, 20 patients affected by bilateral cleft lip and palate, and a control group of 20 subjects with normal occlusion were analyzed for this study. Condylar, ramal, and condylar plus ramal asymmetry indices were measured for all subjects using the method of Habets et al. Kruskal-Wallis and Mann-Whitney tests were used to determine any significant differences between the groups for all indices at the 95% level of confidence. Results: There were no significant differences regarding sex for all mandibular asymmetry indices in all three groups. All Asymmetry indices (condylar, ramal, and condylar plus ramal asymmetry) were significantly higher in the unilateral cleft group compared with the other two groups. Conclusion: Cone beam computed tomography images showed that patients with cleft lip and palate suffered from mandibular asymmetry. Subjects with unilateral cleft lip and palate had a more asymmetric mandible compared with the bilateral cleft lip and palate and control groups. Therefore, the mandible appears to be the leading factor in facial asymmetry in subjects with unilateral cleft lip and palate. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) of the temporomandibular joint (TMJ) is associated with dental biomechanics. A major change during OA progression is the ossification of the osteochondral interface. This study investigated the formation, radiological detectability, and mechanical property of the osteochondral interface at an early stage, the pathogenesis significance of which in OA progression is of clinical interest and remains elusive for the TMJ. Unilateral anterior crossbite (UAC) was performed on 6-wk-old rats as we previously reported. TMJs were harvested at 4, 12, and 20 wk. The progression of TMJ OA was evaluated using a modified Osteoarthritis Research Society International (OARSI) score system. Osteochondral interface was investigated by quantifying the thickness via von Kossa staining of histological slices and in vivo calcium deposition by calcein injection. Tissue ossification was imaged by micro-computed tomography (CT). Mechanical properties were measured at nanoscale using dynamic indentation. Time-dependent TMJ cartilage lesions were elicited by UAC treatment. Geometric change of the condyle head and increased value of the OARSI score were evident in UAC TMJs. At the osteochondral interface, there was not only enhanced deep-zone cartilage calcification but also calcium deposition at the osseous boundary. The thickness, density, and stiffness of the osteochondral interface were all significantly increased. The enhanced ossification of the osteochondral interface is a joint outcome of the aberrant deeper cartilage calcification at the superior region and promoted formation of subchondral cortical bone at the inferior region. The micro-CT detectable ossification from an early stage thus is of diagnostic significance. Although the environment of the cartilage and subchondral bone could be changed due to the stiffness of the interface, whether or not the stiffened interface would accelerate OA progress remains to be confirmed. With that evidence, the osteochondral interface could be a new diagnostic and therapeutic target of the mechanically initiated OA in the TMJ. [ABSTRACT FROM AUTHOR]

Angiogenesis is a complex, multicellular process that is critical for bone development and generation. Endochondral ossification depends on an avascular cartilage template that completely remodels into vascularized bone and involves a dynamic interplay among chondrocytes, osteoblasts, and endothelial cells. We have discovered fibrocartilage stem cells (FCSCs) derived from the temporomandibular joint (TMJ) mandibular condyle that generates cartilage anlagen, which is subsequently remodeled into vascularized bone using an ectopic transplantation model. Here we explore FCSC and endothelial cell interactions during vascularized bone formation. We found that a single FCSC colony formed transient cartilage and host endothelial cells may participate in bone angiogenesis upon subcutaneous transplantation in a nude mouse. FCSCs produced an abundance of the proangiogenic growth factor vascular endothelial growth factor A and promoted the proliferation of human umbilical vein endothelial cells (HUVECs). Using a fibrinogen gel bead angiogenesis assay experiment, FCSC cell feeder layer induced HUVECs to form significantly shorter and less sprouts than D551 fibroblast controls, suggesting that FCSCs may initially inhibit angiogenesis to allow for avascular cartilage formation. Conversely, direct FCSC-HUVEC contact significantly enhanced the osteogenic differentiation of FCSCs. To corroborate this idea, upon transplantation of FCSCs into a bone defect microenvironment, FCSCs engrafted and regenerated intramembranous bone. Taken together, we demonstrate that the interactions between FCSCs and endothelial cells are essential for FCSC-derived vascularized bone formation. A comprehensive understanding of the environmental cues that regulate FCSC fate decisions may contribute to deciphering the mechanisms underlying the role of FCSCs in regulating bone formation. [ABSTRACT FROM AUTHOR]

Temporomandibular joint (TMJ) disorders are often associated with development of osteoarthritis-like changes in the mandibular condyle. Discoidin domain receptor 2 (DDR2), a collagen receptor preferentially activated by type I and III collagen found in the TMJ and other fibrocartilages, has been associated with TMJ degeneration, but its role in normal joint development has not been previously examined. Using Ddr2 LacZ-tagged mice and immunohistochemistry, we found that DDR2 is preferentially expressed and activated in the articular zone of TMJs but not knee joints. To assess the requirement for Ddr2 in TMJ development, studies were undertaken to compare wild-type and smallie ( slie) mice, which contain a spontaneous deletion in Ddr2 to produce an effective null allele. Analysis of TMJs from newborn Ddr2slie/slie mice revealed a developmental delay in condyle mineralization, as measured by micro-computed tomography and histologic analysis. In marked contrast, knee joints of Ddr2slie/slie mice were normal. Analysis of older Ddr2slie/slie mice (3 and 10 mo) revealed that the early developmental delay led to a dramatic and progressive loss of TMJ articular integrity and osteoarthritis-like changes. Mutant condyles had a rough and flattened bone surface, accompanied by a dramatic loss of bone mineral density. Mankin scores showed significantly greater degenerative changes in the TMJs of 3- and 10-mo-old Ddr2slie/slie mice as compared with wild-type controls. No DDR2-dependent degenerative changes were seen in knees. Analysis of primary cultures of TMJ articular chondrocytes from wild-type and Ddr2slie/slie mice showed defects in chondrocyte maturation and mineralization in the absence of Ddr2. These studies demonstrate that DDR2 is necessary for normal TMJ condyle development and homeostasis and that these DDR2 functions are restricted to TMJ fibrocartilage and not seen in the hyaline cartilage of the knee. [ABSTRACT FROM AUTHOR]

Purpose Lateral condyle fractures of the humerus are common in the paediatric population, accounting for up to 20% of elbow fractures. Traditional management involves internal fixation with Kirschner (K)-wires, however, this has been associated with complications and insufficiently rigid fixation. Recently, cannulated screws have been proposed as a more stable method of fixation. While cannulated screws have been thought to allow earlier range of movement and shorten time to union, data regarding the biomechanical performance and optimal screw placement is scarce. We hypothesize that cannulated screw fixation is superior to K-wire fixation and screw placement can enhance the stability of the construct. Methods Paediatric humerus sawbones with Milch II fractures were fixed with one of three methods. Fractures were reduced with either a single cannulated screw either through the centre of the capitellum (oblique), or placed up the lateral column across the growth plate (lateral), or fixed with two K-wires. Fixed sawbone fractures were then mechanically tested in two directions simulating in vivo forces. Results The lateral screw construct had a higher maximum force to failure, higher stiffness and absorbed higher energy as compared with the K-wire fixation and oblique screw under an anterior force. When loaded from the posterior direction, only the lateral column screw was better than K-wire fixation. Conclusions Screw fixation is a biomechanically effective alternative to K-wire fixation, especially when placed up the lateral column of the distal humerus. Further clinical studies are required before transcapitellar screw fixation can be adopted. [ABSTRACT FROM AUTHOR]

Objective:Orthognathic wafers may be made using digital model movements and CAD-CAM technology. This paper analysed the accuracy of maxillary movements using this new process. Design:Retrospective study of pre and post-operative cephalograms. Participants:Thirty consecutive orthognathic patients undergoing bimaxillary osteotomies in a UK hospital. Methods:Jaw movements were planned using cephalometric and Orthoanalyzer™ software. The resultant intermediate and final wafer occlusal relationships were used for wafer fabrication by 3D printing of the inter-occlusal space. Pre- and post-operative lateral cephalograms were compared in terms of maxillary antero-posterior and vertical movements. Statistical analyses including the pairedt-test, two-samplet-test and Fisher’s exact test. Results:Wide individual variation was observed between the planned and actual movements. Thirteen cases (43%) had a 2 mm discrepancy in at least one variable. Statistically significant differences between the planned and actual maxillary vertical movements were observed for the molar (U6y:p< 0.0001) and anterior maxillary (Ay:p< 0.01) differences. Analysis of a subgroup with primarily impaction movements demonstrated a statistically significant bias towards excessive maxillary advancement (U1x:p< 0.01) and incisor impaction (U1y:p< 0.01) in this group. Conclusions:This new digital surgical wafer technique achieves a similar level of accuracy to the conventional facebow and model surgery process. [ABSTRACT FROM AUTHOR]

The mandibular condylar cartilage (MCC) shoulders force for the subchondral bone during mastication. The cartilage matrix contains various large molecules, such as type I, II, and X collagens and proteoglycans (PGs), which jointly play essential roles in maintaining cartilage characteristics. PGs play key roles in maintaining the elasticity of cartilage and providing a cushion against mastication forces. In addition to the well-known PGs, DMP1-PG, which is the PG form of dentin matrix protein 1 (DMP1), is a newly identified PG. DMP1 is proteolytically processed in vivo, and the N-terminus is glycosylated into its PG form-that is, DMP1-PG, which is highly expressed not only in tooth and bone but also in the matrix of the MCC. However, the specific functions of DMP1-PG in the MCC remain unclear. In human temporomandibular joint osteoarthritis and hyperocclusion model rat specimens, PGs are significantly downregulated, and DMP1-PG is the most prominently affected PG. To further investigate the role of DMP1-PG in condylar chondrogenesis, a glycosylation site mutant (S89-G89) mouse model was established with knock-in methods. In the MCC of the S89G-DMP1 mice, the glycosylation level of DMP1 was significantly downregulated, and a series of abnormal developmental and pathologic changes could be observed. The morphologic changes included thinner cartilage layers, deformations of the MCC, and disordered arrangements of the chondrocytes, and an earlier onset of temporomandibular joint osteoarthritis-like changes was observed. In addition, markers of chondrogenesis were downregulated, and the matrix of the MCC displayed OA phenotypes in the S89G-DMP1 mice. Further investigations showed that the transforming growth factor β signaling molecules were affected in the MCC after the loss of DMP1-PG. In addition, the loss of DMP1-PG significantly accelerated the progression of cartilage injuries in the hyperocclusion models. Given these findings, we investigated the significant role of DMP1-PG in the chondrogenesis and maintenance of MCC. [ABSTRACT FROM AUTHOR]

The etiology and treatment of temporomandibular joint (TMJ) osteoarthritis (TMJOA) remain complex and unclear. Based on clinical observations, we hypothesized that low condylar bone quality is significantly correlated with TMJOA and explored this association in a cross-sectional study with human patients. A total of 254 postmenopausal female participants were included in this study. Radiographic findings from cone beam computed tomography (CBCT) and clinical symptoms were used to classify each TMJ data sample as healthy control (n = 124) or TMJOA (n = 130). Condylar bone mineral density (BMD) (computed tomography Hounsfield unit [CT HU]) and bone volume fraction (BV/TV) were measured and modeled as predictors of healthy control versus TMJOA status in multilevel logistic regression analyses. Both CT HU (adjusted odds ratio [AOR] = 0.9989, interquartile odds ratio [IOR] = 0.4206) and BV/TV (AOR= 0.8096, IOR = 0.1769) were negatively associated with TMJOA (P = 0.049, 0.011, respectively). To assess the diagnostic performance of CT HU and BV/TV for identification of TMJOA, receiver operating characteristic (ROC) curves were plotted. The estimated areas under the curve (AUC) were 0.6622 for BV/TV alone, 0.6074 for CT HU alone, and 0.7136 for CT HU and BV/TV together. The model incorporating CT HU and BV/TV together had a significantly higher AUC than the models using BV/TV alone (P = 0.038) or HU alone (P = 0.021). In conclusion, we found that low condylar bone quality was significantly correlated with TMJOA development and that condylar CT HU and BV/TV can be used together as a potential diagnostic tool for TMJOA. Careful clinical evaluation of the condyle coupled with appropriate radiographic interpretation would thus be critical for the early detection of TMJOA. [ABSTRACT FROM AUTHOR]

The temporomandibular joint (TMJ) disc is a heterogeneous fibrocartilaginous tissue positioned between the mandibular condyle and glenoid fossa of the temporal bone, with important roles in TMJ functions. Tissue engineering TMJ discs has emerged as an alternative approach to overcoming limitations of current treatments for TMJ disorders. However, the anisotropic collagen orientation and inhomogeneous fibrocartilaginous matrix distribution present challenges in the tissue engineering of functional TMJ discs. Here, we developed 3-dimensional (3D)-printed anatomically correct scaffolds with region-variant microstrand alignment, mimicking anisotropic collagen alignment in the TMJ disc and corresponding mechanical properties. Connective tissue growth factor (CTGF) and transforming growth factor beta 3 (TGFβ3) were then delivered in the scaffolds by spatially embedding CTGF- or TGFβ3-encapsulated microspheres (µS) to reconstruct the regionally variant fibrocartilaginous matrix in the native TMJ disc. When cultured with human mesenchymal stem/progenitor cells (MSCs) for 6 wk, 3D-printed scaffolds with CTGF/TGFβ3-µS resulted in a heterogeneous fibrocartilaginous matrix with overall distribution of collagen-rich fibrous structure in the anterior/posterior (AP) bands and fibrocartilaginous matrix in the intermediate zone, reminiscent of the native TMJ disc. High dose of CTGF/TGFβ3-µS (100 mg µS/g of scaffold) showed significantly more collagen II and aggrecan in the intermediate zone than a low dose (50 mg µS/g of scaffold). Similarly, a high dose of CTGF/TGFβ3-µS yielded significantly higher collagen I expression in the AP bands compared with the low-dose and empty µS. From stress relaxation tests, the ratio of relaxation modulus to instantaneous modulus was significantly smaller with CTGF/TGFβ3-µS than empty µS. Similarly, a significantly higher coefficient of viscosity was achieved with the high dose of CTGF/TGFβ3-µS compared with the low-dose and empty µS, suggesting the dose effect of CTGF and TGFβ3 on fibrocartilage formation. Together, our findings may represent an efficient approach to engineering the TMJ disc graft with anisotropic scaffold microstructure, heterogeneous fibrocartilaginous matrix, and region-dependent viscoelastic properties. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Increased subchondral trabecular bone turnover due to imbalanced bone-resorbing and bone-forming activities is a hallmark of osteoarthritis (OA). Wnt5a/Ror2 signaling, which can derive from bone marrow stromal cells (BMSCs), takes a role in modulating osteoblast and osteoclast formation. We showed previously that experimentally unilateral anterior crossbites (UACs) elicited OA-like lesions in mice temporomandibular joints (TMJs), displaying as subchondral trabecular bone loss. Herein, we tested the role of BMSC-derived Wnt5a/Ror2 signaling in regulating osteoclast precursor migration and differentiation in this process. The data confirmed the decreased bone mass, increased tartrate-resistant acid phosphatase (TRAP)–positive cell number, and enhanced osteoclast activity in TMJ subchondral trabecular bone of UAC-treated rats. Interestingly, the osteoblast activity in the tissue of TMJ subchondral trabecular bone of these UAC-treated rats was also enhanced, displaying as upregulated expressions of osteoblast markers and increased proliferation, migration, and differentiation capabilities of the locally isolated BMSCs. These BMSCs showed an increased CXCL12 protein expression level and upregulated messenger RNA expressions of Rankl, Wnt5a, and Ror2. Ex vivo data showed that their capacities of inducing migration and differentiation of osteoclast precursors were enhanced, and these enhanced capabilities were restrained after blocking their Ror2 signaling using small interfering RNA (siRNA) assays. Reducing Ror2 expression in the BMSC cell line by siRNA or blocking the downstream signalings with specific inhibitors also demonstrated a suppression of the capacity of the BMSC cell line to promote Wnt5a-dependent migration (including SP600125 and cyclosporine A) and differentiation (cyclosporine A only) of osteoclast precursors. These findings support the idea that Wnt5a/Ror2 signaling in TMJ subchondral BMSCs enhanced by UAC promoted BMSCs to increase Cxcl12 and Rankl expression, in which JNK and/or Ca2+/NFAT pathways were involved and therefore were engaged in enhancing the migration and differentiation of osteoclast precursors, leading to increased osteoclast activity and an overall TMJ subchondral trabecular bone loss in the UAC-treated rats. [ABSTRACT FROM PUBLISHER]

Mandibular condylar cartilage (MCC) is classified as secondary cartilage, the histologic structure of which is unique from that of primary cartilage. MicroRNA (miRNA) is a small noncoding RNA that binds to the messenger RNA (mRNA) target to repress its translation and plays an important role in cell differentiation, proliferation, and death. Microarray analysis revealed that miR-200a was characteristically expressed during embryonic development. We hypothesized that miR-200a may be involved in regulating the formation of cartilage during MCC growth. We investigated the function of miR-200a by transfecting an inhibitor or mimic into MCC organ and cell cultures. A histologic examination revealed the localized inhibitory effects of the miR-200a mimic and widespread enhancing effects of the inhibitor on chondrocytic differentiation in the MCC organ culture system. An immunohistochemical examination and gene expression analysis demonstrated that the miR-200a inhibitor enhanced chondrogenesis, while the mimic had the opposite effect by enhancing cell proliferation. Quantitative reverse transcription polymerase chain reaction analysis revealed that miR-200a downregulated the gene expression of chondrocyte markers. Moreover, transfection of the miR-200a mimic into ATDC5 cells repressed the formation of the cartilaginous matrix. These results indicate that miR-200a contributed to chondrogenesis in developing MCC by controlling proliferation and differentiation in MCC cells. [ABSTRACT FROM PUBLISHER]

Osteoarthritis is a common disease that can cause severe pain and dysfunction in any joint, including the temporomandibular joint (TMJ). TMJ osteoarthritis (TMJOA) is an important subtype in the classification of temporomandibular disorders. TMJOA pathology is characterized by progressive cartilage degradation, subchondral bone remodeling, and chronic inflammation in the synovial tissue. However, the exact pathogenesis and process of TMJOA remain to be understood. An increasing number of studies have recently focused on inflammation and remodeling of subchondral bone during the early stage of TMJOA, which may elucidate the possible mechanism of initiation and progression of TMJOA. The treatment strategy for TMJOA aims at relieving pain, preventing the progression of cartilage and subchondral bone destruction, and restoring joint function. Conservative therapy with nonsteroidal anti-inflammatory drugs, splint, and physical therapy, such as low-energy laser and arthrocentesis, are the most common treatments for TMJOA. These therapies are effective in most cases in relieving the signs and symptoms, but their long-term therapeutic effect on the pathologic articular structure is unsatisfactory. A treatment that can reverse the damage of TMJOA remains unavailable to date. Treatments that prevent the progression of cartilage degradation and subchondral bone damage should be explored, and regeneration for the TMJ may provide the ideal long-term solution. This review summarizes the current understanding of mechanisms underlying the pathogenesis and treatment of TMJOA. [ABSTRACT FROM PUBLISHER]

In temporomandibular joints (TMJs), the disc and condylar cartilage function as load-bearing, shock-absorbing, and friction-reducing materials. The ultrastructure of the TMJ disc and cartilage is different from that of hyaline cartilage in other diarthrodial joints, and little is known about their lubrication mechanisms. In this study, we performed micro-tribometry testing on the TMJ disc and condylar cartilage to obtain their region- and direction-dependent friction properties. Frictional tests with a migrating contact area were performed on 8 adult porcine TMJs at 5 different regions (anterior, posterior, central, medial, and lateral) in 2 orthogonal directions (anterior-posterior and medial-lateral). Some significant regional differences were detected, and the lateral-medial direction showed higher friction than the anterior-posterior direction on both tissues. The mean friction coefficient of condylar cartilage against steel was 0.027, but the disc, at 0.074, displayed a significantly higher friction coefficient. The 2 tissues also exhibited different frictional dependencies on sliding speed and normal loading force. Whereas the friction of condylar cartilage decreased with increased sliding speed and was independent of the magnitude of normal force, friction of the disc showed no dependence on sliding speed but decreased as normal force increased. Further analysis of the Péclet number and frictional coefficients suggested that condylar cartilage relies on interstitial fluid pressurization to a greater extent than the corresponding contact area of the TMJ disc. [ABSTRACT FROM PUBLISHER]

Osterix (Osx) is a transcription factor essential for osteoblast differentiation and bone mineralization. Although there are indications that Osx also plays a regulatory role in cartilage, this has not been well-studied. The goal of this study was to define the function of Osx in the post-natal growth of the secondary cartilage at the mandibular condyle. Conditional Osx knockout (cKO) mice that were missing Osx only in cartilage were generated by crossing Osx-loxP mice to Aggrecan-Cre mice. Cre activity was induced by tamoxifen injection twice a week from day 12 to 1 mo of age, and specimens were collected at 1 and 5 mo of age. At 1 mo of age, the condylar hypertrophic chondrocyte zone in the cKO-mice was > three-fold thicker than that in the age-matched control, with little sign of endochondral bone formation. Immunohistochemistry and analysis of histological data revealed a defect in the coupling of chondrogenesis and osteogenesis in the cKO mice. In five-month-old mice examined to address whether late-stage removal of the Cre-deletion event would alleviate the phenotype, the hypertrophic chondrocyte zone in the cKO condyles was considerably larger than in wild-type mice. There were large discrete areas of calcified cartilage in the hypertrophic zone, few signs of endochondral bone formation, and large regions of disorganized intramembranous bone. Analysis of these data further strengthens the notion that Osterix is essential for the coupling of terminal cartilage differentiation and endochondral ossification in mandibular condylar cartilage. [ABSTRACT FROM PUBLISHER]

Participants: Patients who had undergone comprehensive orthodontic treatment with the skeletally anchored 'Frog' appliance. Methods: 43 participants (20 males and 23 females) who had received treatment with the skeletally anchored 'Frog' appliance where included. In order to explore dentoalveolar and skeletal treatment outcomes, pre- (T1) and post- (T2) treatment measurements were performed on patients' plaster models and cephalometric images. Comparisons between T1 and T2 were made by means of a Student's t-test. All statistical analyses were conducted at the 0.05 level of statistical significance. Results: Study model analysis revealed a statistically significant derotation of maxillary molars (μΔT2-T1=9-5°, P<0.001) as well as an increase in transverse arch dimensions at the end of treatment (μΔT2-T1=2.2 mm, P<0.001). Cephalometric changes included bodily distalization of maxillary molars (μΔ(T2-T1)=-1-9 mm, P<0.001), as well as noticeable angular displacement (μΔT2-T1=4.1°, P=0.004). No significant anchorage loss was observed, as displayed by the limited change in maxillary incisor position (μΔ(T1-T2)==0.2 mm, P=0.45). In addition, excellent vertical control of the maxillary molars was achieved, with no change in the mandibular plane (ML/NSL) angle (μΔT2-T1=0-3°:, P= 0.38). Conclusions: The skeletal 'Frog' is effective in derotating and distalizing maxillary molars without anchorage loss and with excellent vertical control. [ABSTRACT FROM AUTHOR]

We report on the non-surgical management of an adult female whose bilateral mandibular condylar fractures had resulted in a clockwise (posterior) mandibular rotation, limitation of mandibular movements and increased occlusal loading on the molar teeth. She refused maxillary surgery and was treated with a minimally-invasive approach, involving orthodontic fixed appliances and mini-implant intrusion of the maxillary molar teeth. This provided both occlusal and functional improvements. Including a significant increase in the inter-incisal distance, which were stable after one year of retention. [ABSTRACT FROM AUTHOR]

Objective: Insulin-like growth factor (IGF-I) has been used as an indicator of growth hormone levels and hence can also be used as a marker of growth. The main objective of the study was to quantify salivary IGF-I levels and its secretion rate at different quantitative cervical maturation (QCVM) stages and evaluate a possible role for salivary IGF-I in evaluating skeletal growth. Methods: Forty-five subjects (24 female, 21 male) between the ages of 7 and 23 years were included in the study. Each subject had personal information, a lateral cephalogram, and a parotid saliva sample collected on the same day. Results: Salivary IGF-I levels and salivary secretion rates were lowest at QCVM skeletal stages previously associated with the acceleration phase of mandibular growth. Highest levels were found at the high velocity stage. After this there was gradual drop in salivary IGF-I levels and secretion rate at deceleration and completing velocity stages. Relatively high levels in the decelerating velocity stage may be an indication of residual skeletal growth. There was a negative correlation between patient age and levels of IGF-I and its secretion rate, once growth velocity decreased. Conclusions: Salivary IGF-I levels or its secretion rate can be used as an indicator of skeletal growth but longitudinal data are necessary to confirm salivary IGF-I as a marker for skeletal growth prediction and residual mandibular growth. [ABSTRACT FROM AUTHOR]

The Proteoglycan 4 (Prg4) product lubricin plays essential roles in boundary lubrication and movement in limb synovial joints, but its roles in temporomandibular joint (TMJ) are unclear. Thus, we characterized the TMJ phenotype in wild-type and Prg4–/– mouse littermates over age. As early as 2 weeks of age, mutant mice exhibited hyperplasia in the glenoid fossa articular cartilage, articular disc, and synovial membrane. By 1 month of age, there were fewer condylar superficial tenascin-C/Col1-positive cells and more numerous apoptotic condylar apical cells, while chondroprogenitors displayed higher mitotic activity, and Sox9-, Col2-, and ColX-expressing chondrocyte zones were significantly expanded. Mutant subchondral bone contained numerous Catepsin K- expressing osteoclasts at the chondro-osseous junction, increased invasive marrow cavities, and suboptimal subchondral bone. Mutant glenoid fossa, disc, synovial cells, and condyles displayed higher Hyaluronan synthase 2 expression. Mutant discs also lost their characteristic concave shape, exhibited ectopic chondrocyte differentiation, and occasionally adhered to condylar surfaces. A fibrinoid substance of unclear origin often covered the condylar surface. By 6 months of age, mutant condyles displayed osteoarthritic degradation with apical/mid-zone separation. In sum, lubricin exerts multiple essential direct and indirect roles to preserve TMJ structural and cellular integrity over post-natal life. [ABSTRACT FROM PUBLISHER]

Emerging evidence has implied that subchondral bone plays an important role during osteoarthritis (OA) pathology. This study was undertaken to investigate whether abnormalities of the condylar subchondral bone lead to temporomandibular joint (TMJ) OA. We used an osteoblast-specific mutant TGF-β1 transgenic mouse, the CED mouse, in which high levels of active TGF-β1 occur in bone marrow, leading to abnormal bone remodeling. Subchondral bone changes in the mandibular condyles were investigated by micro-CT, and alterations in TMJ condyles were confirmed by histopathological and immunohistochemical analysis. Abnormalities in the condylar subchondral bone, characterized as fluctuant bone mineral density and microstructure and increased but uncoupled activity of osteoclasts and osteoblasts, were apparent in the 1- and 4-month CED mouse groups, while obvious cartilage degradation, in the form of cell-free regions and proteoglycan loss, was observed in the 4-month CED group. In addition, increased numbers of apoptotic chondrocytes and MMP9- and VEGF-positive chondrocytes were observed in the condylar cartilage in the 4-month CED group, but not in the 1-month CED group, compared with their respective age-matched controls. This study demonstrated that progressive degradation of mandibular condylar cartilage could be induced by the abnormal remodeling of the underlying subchondral bone during TMJOA progression. [ABSTRACT FROM PUBLISHER]

In this study, rapid CAD-CAM prototyping of pure hydroxyapatite to replace temporomandibular joint condyles was tested in sheep. Three adult animals were implanted with CAD-CAM-designed porous hydroxyapatite scaffolds as condyle substitutes. The desired scaffold shape was achieved by subtractive automated milling machining (block reduction). Custom-made surgical guides were created by direct metal laser sintering and were used to export the virtual planning of the bone cut lines into the surgical environment. Using the same technique, fixation plates were created and applied to the scaffold pre-operatively to firmly secure the condyles to the bone and to assure primary stability of the hydroxyapatite scaffolds during masticatory function. Four months post-surgery, the sheep were sacrificed. The hydroxyapatite scaffolds were explanted, and histological specimens were prepared. Different histological tissues penetrating the scaffold macropores, the sequence of bone remodeling, new apposition of bone and/or cartilage as a consequence of the different functional anatomic role, and osseointegration at the interface between the scaffold and bone were documented. This animal model was found to be appropriate for testing CAD-CAM customization and the biomechanical properties of porous, pure hydroxyapatite scaffolds used as joint prostheses. [ABSTRACT FROM AUTHOR]

We previously hypothesized that the development of traumatic temporomandibular joint (TMJ) ankylosis was similar to that of hypertrophic non-union. Besides similarities in etiology, hypertrophic bone stumps, and long-term development, the radiolucent zone, frequently located in the ankylosed bone, is another common feature. In this study, we demonstrated that the radiolucent zone also contained multilineage potential cells (RZs, radiolucent-zone-related cells) as the non-union tissues. RZs were characterized and compared with mandibular bone marrow stem cells (BMSCs) by analysis of MSC-related markers, colony-forming-unit assays, multipotential differentiation assays, alkaline phosphatase (ALP) activity assays, and cell transplantation in vivo. Both cell types were positive for CD105, CD166, and Stro-1 expression, negative for CD34 and CD45 expression, and exhibited osteogenic, adipogenic, and chondrogenic differentiation potentials. However, compared with mandibular BMSCs, RZs showed lower colony-forming-unit abilities and proliferation rates. The mineralization and bone-forming ability of RZs was weaker than that of mandibular BMSCs, with Runx2 and ALP mRNA expression and ALP activity significantly lower in RZs. All these results suggest that RZs possess the properties of MSCs but lower proliferation and osteogenic differentiation capacity similar to that of stromal cells in hypertrophic non-union tissues. [ABSTRACT FROM PUBLISHER]

Condylar regeneration with the use of functional appliances after condylectomy has been validated. However, the process during treatment remains unclear. In this study, we evaluated the condylar regeneration process and then examined mandibular growth and masticatory muscle activity after regeneration in growing rats. Seventy-five male Wistar rats aged 4 weeks were equally divided into 3 groups: unilateral condylectomy group, unilateral condylectomy + appliance group, or control group. The use of a functional appliance following condylectomy promoted mandibular growth and regeneration of the condyle 1 week after condylectomy. Condyle regeneration showing normal morphology was finally achieved 8 weeks after condylectomy. Asymmetrical masticatory muscle activity was observed after condylectomy. However, the use of a functional appliance produced symmetrical masticatory muscle activity. These results indicate a favorable regeneration process in the condylectomized area due to the use of a functional appliance. In addition, due to condylar regeneration, symmetrical masticatory muscle activity was achieved. [ABSTRACT FROM PUBLISHER]

Several studies have indicated a positive response of the temporomandibular joint (TMJ) to mandibular advancement, while others have reported that TMJ adaptive responses are non-existent and negligible. Controversy continues to grow over the precise nature of skeletal changes that occur during mandibular growth modification, due to an apparent lack of tissue markers required to substantiate the precise mechanism by which this is occurring. However, evidence suggests that orthopedic forces clinically modify the growth of the mandible. To further our knowledge about the effect of orthopedic treatment on the TMJ, it is necessary that we understand the biologic basis behind the various tissues involved in the TMJ’s normal growth and maturation. The importance of this knowledge is to consider the potential association between TMJ remodeling and mandibular repositioning under orthopedic loading. Considerable histologic and biochemical research has been performed to provide basic information about the nature of skeletal growth modification in response to mandibular advancement. In this review, the relevant histochemical evidence and various theories regarding TMJ growth modification are discussed. Furthermore, different regulatory growth factors and tissue markers, which are used for cellular and molecular evaluation of the TMJ during its adaptive response to biomechanical forces, are underlined. [ABSTRACT FROM PUBLISHER]

We conducted a study to evaluate functional and cosmetic outcomes following reconstruction of the mandibular condyle with direct placement of a vascularized free fibula. We retrospectively reviewed the cases of all patients who had undergone hemimandibulectomy and condyle resection with immediate reconstruction at the Mayo Clinic in Rochester, Minn., between Nov. 1, 2005, and Jan. 31, 2007. We found 7 such cases, all of which occurred in men aged 32 to 61 years (mean: 50.7). Six of these patients had a malignancy and 1 had osteomyelitis. Postoperatively, 6 patients had no difficulty with occlusion, which was rated as "good" or "excellent" at their 6-month follow-up visit; the other patient had an open-bite deformity, but he was able to masticate solid food and maintain an oral diet. Cosmesis was generally satisfactory, and all patients maintained intelligible speech. We conclude that free fibula transfer with direct seating of the fibula into the condylar fossa followed by aggressive physiotherapy provides acceptable functional reconstruction of the mandibulectomycondylectomy defect. [ABSTRACT FROM AUTHOR]

Muenke syndrome is characterized by various craniofacial deformities and is caused by an autosomal-dominant activating mutation in fibroblast growth factor receptor 3 (FGFR3P250R). Here, using mice carrying a corresponding mutation (FgfR3P244R), we determined whether the mutation affects temporomandibular joint (TMJ) development and growth. In situ hybridization showed that FgfR3 was expressed in condylar chondroprogenitors and maturing chondrocytes that also expressed the Indian hedgehog (Ihh) receptor and transcriptional target Patched 1(Ptch1). In FgfR3P244R mutants, the condyles displayed reduced levels of Ihh expression, H4C-positive proliferating chondroprogenitors, and collagen type II- and type X-expressing chondrocytes. Primary bone spongiosa formation was also disturbed and was accompanied by increased osteoclastic activity and reduced trabecular bone formation. Treatment of wild-type condylar explants with recombinant FGF2/FGF9 decreased Ptch1 and PTHrP expression in superficial/polymorphic layers and proliferation in chondroprogenitors. We also observed early degenerative changes of condylar articular cartilage, abnormal development of the articular eminence/glenoid fossa in the TMJ, and fusion of the articular disc. Analysis of our data indicates that the activating FgfR3P244R mutation disturbs TMJ developmental processes, likely by reducing hedgehog signaling and endochondral ossification. We suggest that a balance between FGF and hedgehog signaling pathways is critical for the integrity of TMJ development and for the maintenance of cellular organization. [ABSTRACT FROM PUBLISHER]

The temporomandibular joint (TMJ) is a specialized synovial joint essential for the function of the mammalian jaw. The main components of the TMJ are the mandibular condyle, the glenoid fossa of the temporal bone, and a fibrocartilagenous disc interposed between them. The genetic program for the development of the TMJ remains poorly understood. Here we show the crucial role of sprouty (Spry) genes in TMJ development. Sprouty genes encode intracellular inhibitors of receptor tyrosine kinase (RTK) signaling pathways, including those triggered by fibroblast growth factors (Fgfs). Using in situ hybridization, we show that Spry1 and Spry2 are highly expressed in muscles attached to the TMJ, including the lateral pterygoid and temporalis muscles. The combined inactivation of Spry1 and Spry2 results in overgrowth of these muscles, which disrupts normal development of the glenoid fossa. Remarkably, condyle and disc formation are not affected in these mutants, demonstrating that the glenoid fossa is not required for development of these structures. Our findings demonstrate the importance of regulated RTK signaling during TMJ development and suggest multiple skeletal origins for the fossa. Notably, our work provides the evidence that the TMJ condyle and disc develop independently of the mandibular fossa. [ABSTRACT FROM PUBLISHER]

Restorative dentistry is often performed to treat defects including caries, fractures, access sites for endodontic therapy, and enamel lesions. Restorative materials can reestablish tooth function, restore esthetics, or do both. The objectives of restorative dentistry are to return (restore) teeth to optimum form and function, prevent further breakdown of the remaining tooth structure, to protect pulp tissue from thermal, mechanical, and bacterial insult, and to create a proper or aesthetic tooth appearance. Enamel defects in dogs can affect one or multiple teeth. This case report will focus on a single enamel defect affecting the non-occlusal surface of a mandibular first molar tooth. This case report includes descriptions of proper defect preparation and application of a flowable composite, and a review of composite materials used in restorative dentistry. [ABSTRACT FROM AUTHOR]

Primary cilia regulate limb and axial skeletal formation and hedgehog signaling, but their roles in temporomandibular joint (TMJ) development are unknown. Thus, we created conditional mouse mutants deficient in ciliary transport protein Kif3a in cartilage. In post-natal wild-type mice, primary cilia were occasionally observed on the superior, inferior, or lateral side of condylar cells. Cilia were barely detectable in mutant chondrocytes but were evident in surrounding tissues, attesting to the specificity of chondrocyte Kif3a ablation. Mutant condyles from 3-month-old mice were narrow and flat along their antero-posterior and medio-lateral axes, were often fused with the articular disc, and displayed an irregular bony surface. The polymorphic layer in P15 mutants contained fewer Sox9-expressing chondroprogenitor cells because of reduced mitotic activity, and newly differentiated chondrocytes underwent precocious hypertrophic enlargement accompanied by early activation of Indian hedgehog (Ihh). Interestingly, there was excessive intramembranous ossification along the perichondrium, accompanied by local expression of the hedgehog receptor Patched-1 and up-regulation of Osterix and Collagen I. In summary, Kif3a and primary cilia are required for coordination of chondrocyte maturation, intramembranous bone formation, and chondrogenic condylar growth. Defects in these processes in Kif3a condylar cartilage are likely to reflect abnormal hedgehog signaling topography and dysfunction. [ABSTRACT FROM PUBLISHER]

A 12-week-old kitten was presented for symphyseal separa-tion, comminuted rostral fractures of the mandibles, avul-sion of the mandibular lip, and fractured teeth. Oral exami-nation and intraoral dental radiographs demonstrated a mandibular symphyseal separation and the presence of developing tooth buds. Cerclage wire was placed circum-ferentially around the mandibles for 2-weeks to provide stabilization of the mandibular symphyseal separation. Clinical examination 9.5-months following surgery demon-strated normal occlusion with enamel hypoplasia affecting the mandibular canine teeth. Intraoral dental radiographs showed a partial bony union of the mandibular symphysis and vital, developing mandibular canine teeth. [ABSTRACT FROM AUTHOR]

This study aimed to develop a plate to treat fractures of the mandibular body in dogs and to validate the project using finite elements and biomechanical essays. Mandible proto-types were produced with 10 oblique ventrorostral fractures (favorable) and 10 oblique ventrocaudal fractures (unfavor-able). Three groups were established for each fracture type. Osteosynthesis with a pure titanium plate of double-arch geometiy and blocked monocortical screws of free angula-tion were used. The mechanical resistance of the prototype with unfavorable fracture was lower than that of the favorable fracture. In both fractures, the deflection increased and the relative stiffness decreased proportionally to the diminishing screw number. The finite element analysis validated this plate study, since the maximum tension concentration observed on the plate was lower than the resistance limit tension admitted by the titanium. In conclusion, the double-arch geometry plate fixed with blocked monocortical screws has sufficient resis-tance to stabilize oblique fractures, without compromising mandibular dental or neurovascular structures. [ABSTRACT FROM AUTHOR]

Objective: We present the short-term treatment results of a modified technique in transoral endoscopic condyle repair. Design: A pilot prospective study from April 2006 to November 2007. Setting: Ankara University Medical School Teaching Hospital. Methods: Four patients with subcondylar fracture were treated with transoral endoscopic condyle repair. Preliminary restoration of the occlusion was provided with maxillomandibular fixation. Four hands endoscopic sinus surgery principles were adapted to transoral endoscopic condyle repair. Main Outcome Measures: Providing condylar stabilization with good occlusion and temporomandibular joint function was expected from treatment. Results: Open reduction and internal fixation were achieved in all patients. Condylar stabilization was confirmed by intraoperative endoscopic findings and postoperative panoramic radiographs. Uneventful healing with good occlusion and temporomandibular joint function were noted in 3 to 14 months of follow-up. Conclusion: Endoscope-assisted minimal invasive procedures have been taking more part in head and neck soft tissue and trauma surgery. The cost of instruments and technical difficulties are the main constraints of endoscopic techniques. In this study, we present a practical way to perform transoral endoscopic condyle repair using the otolaryngologist's standard sinus surgery endovisual equipment and a titanium miniplate system. With the addition of a surgical hand, successful treatment results could be achieved with reduced cost. [ABSTRACT FROM AUTHOR]

Background: The cause of osteochondritis dissecans (OCD) is unknown, but mechanical factors seem to play a role. Purpose: To identify a relationship between localization of OCD and mechanical axis of the leg. Study Design: Case series; Level of evidence, 4. Methods: Using bilateral full-leg standing radiographs, we analyzed the position of the mechanical axis of the leg in a group of 93 adolescent and adult patients (103 knees) with OCD of the medial or lateral femoral condyle. Results: The location of OCD and the position of the mechanical axis in the same knee compartment was significantly correlated for both knees with medial (P < .001) as well as lateral (P < .012) compartment OCD. In the medial OCD group, the mean mechanical axis was located in the medial knee compartment (28% medial ± 2.8%; range, 100% medial to 14% lateral) with a statistically insignificant medial shift with respect to the unaffected side. In lateral OCD, the mean mechanical axis was located laterally (13% lateral ± 3.9%; range, 13% medial to 60% lateral) with a significant shift from the medial into the lateral knee compartment when comparing unaffected with affected knees. No significant difference was observed between adolescents with open growth plates compared with adults with closed growth plates (P > .05). Conclusion: We found an association between medial condyle OCD and varus axis and between lateral condyle OCD and valgus axis. This evokes higher loading of the affected than of the unaffected knee compartment, and therefore, axial alignment may be a cofactor in OCD of the femoral condyles. [ABSTRACT FROM AUTHOR]

Objective: To describe craniofacial morphology in children from families with the mitochondrial encephalomyopathy, lactic acidosis, stroke-like episodes (MELAS) syndrome. Design: Transversal prospective case-control study from a tertiary center. Subjects: Nine children (five girls, four boys; aged 7.5 to 15.3 years) of mothers with m.3243A.G mutation in mitochondrial DNA and 36 age- and sexmatched healthy children as controls. Methods: Seventy-three cephalometric variables representing craniofacial and dental features were analyzed in lateral radiographs. The statistical dependence caused by intrafamilial correlation was taken into account by using a two-level analysis of variance model that was fitted to the data using SAS procedure MIXED. Results: The frontal bone was thicker and the frontal sinus, mandibular symphysis width, and lower posterior face height were larger in the subjects than in the controls. Upper incisors were more labially inclined, and the interincisal angle was smaller in subjects than in the control children. Conclusions: Differences were found in craniofacial structures between the children of mothers with m.3243A.G and unaffected children. Differences in the upper incisor inclination, mandibular symphysis width, and lower posterior face height suggest an altered mandibular growth pattern in the subjects. In addition, the children had cranial aberrations such as larger frontal sinuses and the thicker frontal bone. [ABSTRACT FROM AUTHOR]

Intermittent parathyroid hormone (PTH) administration has been shown to be a promising therapy for systemic bone loss. Accordingly, we hypothesized that PTH could have positive results in treating oral complications of osteoporosis. Hence, we evaluated both mandibular bone loss and its response to PTH in a rabbit model of osteoporosis induced by ovariectomy and glucocorticoid administration. There was a significant and marked decrease in bone mineral density (BMD), bone mineral content (BMC), and calcium content in ash from the osteoporotic peri-alveolar region, which influenced global jaw loss. Remarkably, PTH (1-34) administration to osteoporotic rabbits almost completely reversed BMD, BMC, and calcium content fall in the peri-alveolar region, subsequently reducing global mandibular bone loss. Thus, although the peri-alveolar region is particularly susceptible to osteoporosis, it also responds well to intermittent PTH. Therefore, these results suggest that PTH might represent a valid therapy for improving the osseointegration of dental implants in persons with osteoporosis. [ABSTRACT FROM AUTHOR]

Indian hedgehog (Ihh) is essential for embryonic mandibular condylar growth and disc primordium formation. To determine whether it regulates those processes during post-natal life, we ablated Ihh in cartilage of neonatal mice and assessed the consequences on temporomandibular joint (TMJ) growth and organization over age. Ihh deficiency caused condylar disorganization and growth retardation and reduced polymorphic cell layer proliferation. Expression of Sox9, Runx2, and Osterix was low, as was that of collagen II, collagen I, and aggrecan, thus altering the fibrocartilaginous nature of the condyle. Though a disc formed, it exhibited morphological defects, partial fusion with the glenoid bone surface, reduced synovial cavity space, and, unexpectedly, higher lubricin expression. Analysis of the data shows, for the first time, that continuous Ihh action is required for completion of post-natal TMJ growth and organization. Lubricin overexpression in mutants may represent a compensatory response to sustain TMJ movement and function. [ABSTRACT FROM AUTHOR]