Diagnostic index of three-dimensional osteoarthritic changes in temporomandibular joint condylar morphology.
ABSTRACT: This study aimed to investigate imaging statistical approaches for classifying three-dimensional (3-D) osteoarthritic morphological variations among 169 temporomandibular joint (TMJ) condyles. Cone-beam computed tomography scans were acquired from 69 subjects with long-term TMJ osteoarthritis (OA), 15 subjects at initial diagnosis of OA, and 7 healthy controls. Three-dimensional surface models of the condyles were constructed and SPHARM-PDM established correspondent points on each model. Multivariate analysis of covariance and direction-projection-permutation (DiProPerm) were used for testing statistical significance of the differences between the groups determined by clinical and radiographic diagnoses. Unsupervised classification using hierarchical agglomerative clustering was then conducted. Compared with healthy controls, OA average condyle was significantly smaller in all dimensions except its anterior surface. Significant flattening of the lateral pole was noticed at initial diagnosis. We observed areas of 3.88-mm bone resorption at the superior surface and 3.10-mm bone apposition at the anterior aspect of the long-term OA average model. DiProPerm supported a significant difference between the healthy control and OA group ([Formula: see text]). Clinically meaningful unsupervised classification of TMJ condylar morphology determined a preliminary diagnostic index of 3-D osteoarthritic changes, which may be the first step towards a more targeted diagnosis of this condition.
Project description:There are limited clinical treatments for temporomandibular joint (TMJ) pathologies, including degenerative disease, disc perforation and heterotopic ossification (HO). One barrier hindering the development of new therapies is that animal models recapitulating TMJ diseases are poorly established. The objective of this study was to develop an animal model for TMJ cartilage degeneration and disc pathology, including disc perforation and soft tissue HO.New Zealand white rabbits (n = 9 rabbits) underwent unilateral TMJ disc perforation surgery and sham surgery on the contralateral side. A 2.5 mm defect was created using a punch biopsy in rabbit TMJ disc. The TMJ condyles and discs were evaluated macroscopically and histologically after 4, 8 and 12 weeks. Condyles were blindly scored by four independent observers using OARSI recommendations for macroscopic and histopathological scoring of osteoarthritis (OA) in rabbit tissues.Histological evidence of TMJ condylar cartilage degeneration was apparent in experimental condyles following disc perforation relative to sham controls after 4 and 8 weeks, including surface fissures and loss of Safranin O staining. At 12 weeks, OARSI scores indicated experimental condylar cartilage erosion into the subchondral bone. Most strikingly, HO occurred within the TMJ disc upon perforation injury in six rabbits after 8 and 12 weeks.We report for the first time a rabbit TMJ injury model that demonstrates condylar cartilage degeneration and disc ossification, which is indispensible for testing the efficacy of potential TMJ therapies.
Project description:Angiogenesis has been reported participated in temporomandibular joint osteoarthritis (TMJ-OA). While the pathogenesis is unclear, recent studies indicate that hypoxia is important in TMJ-OA. In order to induce osteoarthritis-like lesions in mandibular condyles, rats were sleep deprived experimentally. An increased number of blood vessels were observed in the rats' condyles of SD and SR group compared with controls. Protein and mRNA levels of related factors including VEGF, HIF-1 and Notch were investigated by means of immunohistochemical staining, western blot and real-time PCR, which were highly expressed in the TMJ-OA rats. Furthermore, Cell test was designed to study effects of hypoxia on condylar chondrocytes. We found the expression of VEGF, HIF-1 and Notch were significantly increased in hypoxia group, indicating that HIF-1-Notch-VEGF signaling pathway were activated by hypoxia. The inhibitors of HIF-1 and Notch could suppress the expression of HIF-1, VEGF, Notch, suggesting the HIF-1-VEGF-Notch signaling pathway were bidirectional. Together, hypoxia played an important role in TMJ-OA and accelerates angiogenesis of condylar cartilage through HIF-1-VEGF-Notch signaling pathway. HIF-1? and Notch might be novel therapeutic targets in TMJ-OA.
Project description: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.
Project description:The temporomandibular joint (TMJ) functions as a load-bearing diarthrodial joint during mastication, and its continuous use and stress can lead to degeneration over age. Using senescence-accelerated (SAMP8) mice that develop early osteoarthritis-like changes in synovial joints at high frequency, we analyzed possible molecular mechanisms of TMJ degeneration and tested whether and how malocclusion may accelerate it. Condylar articular cartilage in young SAMP8 mice displayed early-onset osteoarthritic changes that included reductions in superficial/chondroprogenitor cell number, proteoglycan/collagen content, and Indian hedgehog (Ihh)-expressing chondrocytes. Following malocclusion induced by tooth milling, the SAMP8 condyles became morphologically defective, displayed even lower proteoglycan levels, and underwent abnormal chondrocyte maturation compared with malocclusion-treated condyles in wild-type mice. Malocclusion also induced faster progression of pathologic changes with increasing age in SAMP8 condyles as indicated by decreased PCNA-positive proliferating chondroprogenitors and increased TUNEL-positive apoptotic cells. These changes were accompanied by steeper reductions in Ihh signaling and by expression of matrix metalloproteinase 13 at the chondro-osseous junction in SAMP8 articular cartilage. In sum, we show for the first time that precocious TMJ degeneration in SAMP8 mice is accompanied by--and possibly attributable to--altered Ihh signaling and that occlusal dysfunction accelerates progression toward degenerative TMJ disease in this model.
Project description:We assessed the pathological changes of articular cartilage and subchondral bone on different locations of the knee after extracorporeal shockwave therapy (ESWT) in early osteoarthritis (OA). Rat knees under OA model by anterior cruciate ligament transaction (ACLT) and medial meniscectomy (MM) to induce OA changes. Among ESWT groups, ESWT were applied to medial (M) femur (F) and tibia (T) condyles was better than medial tibia condyle, medial femur condyle as well as medial and lateral (L) tibia condyles in gross osteoarthritic areas (p<0.05), osteophyte formation and subchondral sclerotic bone (p<0.05). Using sectional cartilage area, modified Mankin scoring system as well as thickness of calcified and un-calcified cartilage analysis, the results showed that articular cartilage damage was ameliorated and T+F(M) group had the most protection as compared with other locations (p<0.05). Detectable cartilage surface damage and proteoglycan loss were measured and T+F(M) group showed the smallest lesion score among other groups (p<0.05). Micro-CT revealed significantly improved in subchondral bone repair in all ESWT groups compared to OA group (p<0.05). There were no significantly differences in bone remodeling after ESWT groups except F(M) group. In the immunohistochemical analysis, T+F(M) group significant reduced TUNEL activity, promoted cartilage proliferation by observation of PCNA marker and reduced vascular invasion through observation of CD31 marker for angiogenesis compared to OA group (P<0.001). Overall the data suggested that the order of the effective site of ESWT was T+F(M) ? T(M) > T(M+L) > F(M) in OA rat knees.
Project description:Biomarkers of temporomandibular joint (TMJ) osteoarthritis (OA) remain unknown. The objective was to detect whether molecular biomarkers from peripheral blood leucocytes (PBLs) engage in TMJ OA lesions. Thirty-four six-week-old Sprague Dawley rats were used. The top upregulated gene ontology categories and gene-fold changes in PBLs were detected by a microarray analysis comparing rats that received 20-week unilateral anterior crossbite (UAC) treatment with age-matched controls (n = 4). Twenty weeks of UAC treatment had been reported to induce TMJ OA-like lesions. The other twenty-four rats were randomly placed in the UAC and control groups at 12- and 20-week time points (n = 6). The mRNA expression levels of the selected biomarkers derived from the microarray analysis and their protein expression in the alveolar bone and TMJ were detected. The microarray analysis indicated that the three most highly involved genes in PBLs were Egr1, Ephx1 and Il10, which were confirmed by real-time PCR detection. The increased protein expression levels of the three detected molecules were demonstrated in cartilage and subchondral bone (P < 0.05), and increased levels of EPHX1 were reported in discs (P < 0.05); however, increased levels were not present in the alveolar bone. Immunohistochemistry revealed the increased distribution of EGR1-positive, EXPH1-positive and IL10-positive cells predominantly in the osteochondral interface, with EXPH1 also present in TMJ discs. In conclusion, the increased mRNA expression of Egr1, Ephx1 and Il10 in PBLs may serve as potential biomarkers for developed osteoarthritic lesions relating to osteochondral interface hardness changes induced by dental biomechanical stimulation.
Project description:Temporo-mandibular osteo arthritis (TMJ OA) is characterized by progressive cartilage degradation and subchondral bone remodeling. The causes of this pathology remain unclear. Current research efforts are concentrated in finding new biomarkers that will help us understand disease progression and ultimately improve the treatment of the disease. In this work, we present Shape Variation Analyzer (SVA), the goal is to develop a noninvasive technique to provide information about shape changes in TMJ OA. SVA uses neural networks to classify morphological variations of 3D models of the mandibular condyle. The shape features used for training include normal vectors, curvature and distances to average models of the condyles. The selected features are purely geometric and are shown to favor the classification task into 6 groups generated by consensus between two clinician experts. With this new approach, we were able to accurately classify 3D models of condyles. In this paper, we present the methods used and the results obtained with this new tool.
Project description:Pathological changes and resulting functional impairment of the temporomandibular joint (TMJ) can substantially affect physical condition, morbidity, and mortality of wildlife species. Analysis of TMJ disorders is therefore of interest for the characterization of the health status of populations of wild mammals. This paper, for the first time, analyses the prevalence of TMJ osteoarthritis (TMJ-OA) and the spectrum of osteoarthritic bone lesions of the TMJ in the Eastern Atlantic harbour seal (Phoca vitulina vitulina), applying a standardized scoring system. Dry skulls of 1872 individuals from the German North Sea, collected between 1961 and 1994, were examined for lesions consistent with a diagnosis of TMJ-OA. Of the skulls, 913 (48.8%) were from male, 959 (51.2%) from female seals, with age at death ranging from 2 weeks to 25 years. Possible associations of TMJ-OA with dental or periodontal disorders were also analysed.Lesions consistent with TMJ-OA were found in 963 (53.9%) of the 1787 juvenile/subadult (5 weeks to 5 years of age) and adult (>?5 years) specimens, the condition mostly (95.0% of affected individuals) occurring in a bilateral fashion. Males were affected more frequently than females (p <?0.001), while lesion severity tended to be higher in females (p <?0.05). Severity of TMJ-OA lesions was positively correlated with age (p <?0.001). Lesion severity was also weakly positively correlated with the number of fractured teeth (p <?0.05) and of intravitally lost teeth (p <?0.01), when controlling for age at death as a confounder.TMJ-OA is a common disorder in the Eastern Atlantic harbour seal. The more pronounced severity of the lesions in females compared to males is basically attributed to the higher average age of the female subsample. The causes underlying the high prevalence of TMJ-OA in the studied assemblage remain unknown. Most of the specimens (75.3%) analysed in the present study were found dead during the first phocine distemper virus epizootic in 1988. Therefore, it is assumed that, contrary to other museum collections, only little overrepresentation of pathological skeletal conditions is present in this death sample compared with the population from which it originated.
Project description:Bone loss due to smoking represents a major risk factor for fractures and bone osteoporosis. Signaling through the aryl hydrocarbon receptor (AhR) and its ligands contributes to both bone homeostasis and inflammatory diseases. It remains unclear whether the same AhR signaling axis affects the temporomandibular joint (TMJ). The aim of this study was to investigate possible mechanisms which mediate bone loss in the TMJ due to smoking. In particular, whether benzo[a]pyrene (B[a]P), a carcinogen of tobacco smoke, induces expression of the AhR target gene, Cyp1a1, in mandibular condyles. Possible functions of an endogenous ligand of FICZ, were also investigated in a TMJ-osteoarthritis (OA) mouse model. B[a]P was administered orally to wild-type and AhR<sup>-/-</sup> mice and bone metabolism was subsequently examined. TMJ-OA was induced in wild-type mice with forceful opening of the mouth. Therapeutic functions of FICZ were detected with μCT and histology. Exposure to B[a]P accelerated bone loss in the mandibular subchondral bone. This bone loss manifested with osteoclastic bone resorption and upregulated expression of Cyp1a1 in an AhR-dependent manner. In a mouse model of TMJ-OA, FICZ exhibited a dose-dependent rescue of mandibular subchondral bone loss by repressing osteoclast activity. Meanwhile, in vitro, pre-treatment with FICZ reduced RANKL-mediated osteoclastogenesis. B[a]P regulates mandibular subchondral bone metabolism via the Cyp1a1. The AhR ligand, FICZ, can prevent TMJ-OA by regulating osteoclast differentiation.
Project description:The aim of this article is to review temporomandibular joint symptoms as well as the effects of orthognathic surgery(OGS) on temporomandibular joint(TMJ). The causes of temporomandibular joint disease(TMD) are multifactorial, and the symptoms of TMD manifest as a limited range of motion of mandible, pain in masticatory muscles and TMJ, Joint noise (clicking, popping, or crepitus), myofascial pain, and other functional limitations. Treatment must be started based on the proper diagnosis, and almost symptoms could be subsided by reversible options. Minimally invasive options and open arthroplasty are also available following reversible treatment when indicated. TMD manifesting in a variety of symptoms, also can apply abnormal stress to mandibular condyles and affect its growth pattern of mandible. Thus, adaptive developmental changes on mandibular condyles and post-developmental degenerative changes of mandibular condyles can create alteration on facial skeleton and occlusion. The changes of facial skeleton in DFD patients following OGS have an impact on TMJ, masticatory musculature, and surrounding soft tissues, and the changes of TMJ symptoms. Maxillofacial surgeons must remind that any surgical procedures involving mandibular osteotomy can directly affect TMJ symptoms, thus pre-existing TMJ symptoms and diagnoses should be considered prior to treatment planning and OGS.