Automatic detection of anteriorly displaced temporomandibular joint discs on magnetic resonance images using a deep learning algorithm.

OBJECTIVES: This study aimed to develop models that can automatically detect anterior disc displacement (ADD) of the temporomandibular joint (TMJ) on MRIs before orthodontic treatment to reduce the risk of developing serious complications after treatment. METHODS: We used 9009 sagittal MRI of the TMJ as input and constructed three sets of deep learning models to detect ADD automatically. Deep learning models were developed using a convolutional neural network (CNN) based on the ResNet architecture and the "Imagenet" database. Five-fold cross-validation, oversampling, and data augmentation techniques were applied to reduce the risk of overfitting the model. The accuracy and area under the curve (AUC) of the three models were compared. RESULTS: The performance of the maximum open mouth position model was excellent with accuracy and AUC of 0.970 (±0.007) and 0.990 (±0.005), respectively. For closed mouth position models, the accuracy and AUC of diagnostic Criteria 1 were 0.863 (±0.008) and 0.922 (±0.009), respectively significantly higher than that of diagnostic Criteria 2 with 0.839 (±0.013) (p = 0.009) and AUC of 0.885 (±0.018) (p = 0.003). The classification activation heat map also improved our understanding of the models and visually displayed the areas that play a key role in the model recognition process. CONCLUSION: Our CNN model resulted in high accuracy and AUC in detecting ADD and can therefore potentially be used by clinicians to assess ADD before orthodontic treatment, and hence improve treatment outcomes.

Low-intensity pulsed ultrasound inhibits IL-6 in subchondral bone of temporomandibular joint osteoarthritis by suppressing the TGF-ß1/Smad3 pathway.

OBJECTIVE: This study aimed to provide further information on the exact mechanisms involved in the anti-inflammatory effect of low-intensity pulsed ultrasound (LIPUS) on rabbit temporomandibular joint osteoarthritis (TMJOA) on interleukin-6 (IL-6) production in subchondral bone, IL-6 production in IL-1ß stimulated via inhibition of the TGF-ß1/Smad3 pathway in mouse embryo osteoblast precursor (MC3T3-E1) cells. DESIGN: Bilateral joints were injected with type II collagenase to establish TMJOA models in two male and four female rabbits. The left joint was continuously stimulated by LIPUS, while the right joint was treated with the power off in this model. One male and two female rabbits were used as normal healthy controls without treatment. The histological features of subchondral bone were examined by Safranin-O/Fast staining. Immunohistochemistry was conducted to evaluate IL-6 expression. Then, cells were stimulated by LIPUS with IL-1ß. IL-6 expression and activity of the TGF-ß1/Smad3 pathway were evaluated by Enzyme-linked immunosorbent assay (ELISA), Immunofluorescence and Western blotting, respectively. Specific inhibition of the TGF-ß1/Smad3 pathway was conducted by transfecting with small interfering RNA (siRNA) of type II receptor (siTßRII). RESULTS: LIPUS significantly ameliorated the production of IL-6 in vitro and in vivo. Its inhibitory effect on the production of IL-6 induced by IL-1ß in MC3T3-E1 cells was partly reversed by siTßRII knockdown. CONCLUSIONS: LIPUS inhibited IL-6 production by suppressing the TGF-ß1/Smad3 pathway of subchondral bone in TMJOA. These data revealed the part of the pathways involved in the anti-inflammatory effect of LIPUS and provided a possible treatment strategy for TMJOA patients and other inflammatory diseases.

Overexpression of HIF-1alpha in Bone Marrow Mesenchymal Stem Cells Promote the Repair of Mandibular Condylar Osteochondral Defect in a Rabbit Model.

PURPOSE: The self-repair ability of temporomandibular joint (TMJ) cartilage is limited. Hypoxia-inducible factor-1 alpha (HIF-1alpha) may induce stem cells to promote chondrogenic repair. The purpose of this study was to systematically evaluate the effect of HIF-1alpha overexpression in bone marrow mesenchymal stem cells (BMSCs) combined with collagen scaffolds on the repair of TMJ condylar osteochondral defects in a rabbit model. METHODS: Osteochondral defects of 3-mm diameter × 2-mm depth were created at the right side of the mandibular condyle in 40 New Zealand white rabbits. The defect sites were treated with simple empty, collagen scaffolds (COL), BMSCs/COL, and HIF-1alpha overexpression BMSCs/COL groups. The histomorphologic features of condylar cartilage were monitored by gross examination, safranin O-fast green staining (Solarbio, Beijing, China), and immunohistochemical staining. The changes in subchondral bone were examined by microcomputed tomography. Immunofluorescence staining was used to trace the transplanted BMSCs in vivo. RESULTS: At 12 weeks postimplantation, histologic staining showed that the osteochondral defects in the simple empty and COL groups were mainly filled with fibrous tissue, whereas the BMSCs/COL and HIF-1alpha overexpression BMSCs/COL groups repaired the defect with fibrocartilage. Furthermore, the cartilage was better organized in the HIF-1alpha overexpression BMSCs/COL group compared with the BMSCs/COL group. Microcomputed tomography showed that osteochondral defects can cause abnormal hyperosteogeny in subchondral bone, and the transplantation of BMSCs, especially HIF-1alpha overexpression BMSCs, may alleviate osteosclerosis. Immunofluorescence staining showed that HIF-1alpha overexpression can promote the survival of transplanted BMSCs. CONCLUSIONS: The transplantation of HIF-1alpha overexpression BMSCs combined with a COL scaffold promotes cartilaginous repair of condylar cartilage and inhibits subchondral bone sclerosis in TMJ condylar osteochondral defect rabbits.

Targeting EZH2 Ameliorates the LPS-Inhibited PDLSC Osteogenesis via Wnt/ß-Catenin Pathway.

As a histone methyltransferase, enhancer of zeste homolog 2 (EZH2), suppresses osteoblast maturation and is involved in inflammation. However, the role of EZH2 in human periodontal ligament stem cells (PDLSCs) under inflammation still needs to be further investigated. This study aimed to identify the underlying mechanisms and explore the function of EZH2 in PDLSC osteogenesis under inflammation. PDLSCs were treated with sh-EZH2, DZNep or DKK1 under inflammation. The alkaline phosphatase (ALP) activity, alizarin red staining, and osteogenesis-related protein levels were analyzed. Lipopolysaccharide (LPS)-induced inflammation restrained osteogenic differentiation. Under inflammation, the upregulation of EZH2 suppressed the expression of osteogenic markers, including osteocalcin, runt-related transcription factor 2, and bone morphogenetic protein-2, the activity of ALP, and the accumulation of mineralization through the Wnt/ß-catenin pathway. EZH2 knockdown inhibited the levels of proinflammatory cytokines such as interleukin-6 and tumor necrosis factor-α. These results suggested that LPS-induced overexpression of EZH2 suppressed PDLSC osteogenesis under inflammatory conditions through the Wnt/ß-catenin pathway. These findings give new insights into the physiological differentiation and pathological inflammation of PDLSC osteogenesis, and provide an underlying therapeutic target for periodontitis.