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Tooth ankylosis is a pathological condition of periodontal ligament (PDL) restoration after tooth replantation. Platelet-derived growth factor-BB (PDGF-BB) has been proposed as a promising factor for preventing tooth ankylosis. Using rat tooth replantation model, we investigated whether PDGF-BB accelerates the repair of PDL after tooth replantation without ankylosis, and its molecular mechanisms. In PDGF-BB pretreated replanted teeth (PDGF-BB group), ankylosis was markedly reduced and functionally organized PDL collagen fibers were restored; the mechanical strength of the healing PDL was restored to an average of 76% of that in non-replanted normal teeth at 21 days. The numbers of PDGF-Rβ- and BrdU-positive cells in the periodontal tissues of the PDGF-BB group were greater than those of atelocollagen pretreated replanted teeth (AC group). Moreover, in the PDGF-BB group, the periodontal tissues had fewer osteocalcin-positive cells and decreased number of nuclear β-catenin-positive cells compared to those in the AC group. In vitro analyses showed that PDGF-BB increased the proliferation and migration of human periodontal fibroblasts. PDGF-BB downregulated mRNA expressions of RUNX2 and ALP, and inhibited upregulatory effects of Wnt3a on β-catenin, AXIN2, RUNX2, COL1A1, and ALP mRNA expressions. These findings indicate that in tooth replantation, topical PDGF-BB treatment enhances cell proliferation and migration, and inhibits canonical Wnt signaling activation in bone-tooth ankylosis, leading to occlusal loading of the PDL tissues and subsequent functional restoration of the healing PDL. This suggests a possible clinical application of PDGF-BB to reduce ankylosis after tooth replantation and promote proper regeneration of PDL.

Parathyroid hormone 1 receptor (PTH1R) signaling is critical for mineral ion homeostasis and skeletal development. Although its role in tooth root formation and eruption is established, its specific functions in adult periodontal tissues and craniofacial integrity remain incompletely defined. Here, we investigated the craniofacial and dentoalveolar phenotypes of mice with conditional deletion of PTH1R in DMP1-Cre-expressing cells. DMP1-Cre;PTH1R mutant mice exhibited craniofacial alterations, including reduced maxillary length and defects in the alveolar bone surrounding the molars, as revealed by micro-computed tomography and histological analysis. The mutant mice also displayed severe periodontal ligament (PDL) loss and extensive molar ankylosis, characterized by the direct fusion of alveolar bone to tooth roots, predominantly in regions of acellular cementum. In contrast, incisor development remained unaffected. PTH1R deficiency also resulted in pathological cementum overgrowth, disrupted PDL fiber organization, and decreased expression of key PDL matrix proteins, as evidenced by immunohistochemical and molecular analyses. Mechanistically, the loss of PTH1R enhanced Smad3 phosphorylation and upregulated Osterix, thereby promoting aberrant cementoblast differentiation and mineralization. Concurrently, Dkk1 expression was increased, leading to suppressed Wnt signaling. This evidence establishes PTH1R signaling in cementocytes as a central safeguard of cementum homeostasis and PDL integrity and demonstrates that its disruption induces pathological root-bone fusion and craniofacial abnormalities. These findings advance our understanding of the molecular mechanisms underlying adult periodontal tissue maintenance and open new opportunities for developing therapeutic strategies against ankylosis and related disorders by targeting PTH1R signaling.

Objectives To evaluate the feasibility and diagnostic accuracy of a deep learning network for detection of structural lesions of sacroiliitis on multicentre pelvic CT scans. Methods Pelvic CT scans of 145 patients (81 female, 121 Ghent University/24 Alberta University, 18–87 years old, mean 40 ± 13 years, 2005–2021) with a clinical suspicion of sacroiliitis were retrospectively included. After manual sacroiliac joint (SIJ) segmentation and structural lesion annotation, a U-Net for SIJ segmentation and two separate convolutional neural networks (CNN) for erosion and ankylosis detection were trained. In-training validation and tenfold validation testing (U-Net— n  = 10 × 58; CNN— n  = 10 × 29) on a test dataset were performed to assess performance on a slice-by-slice and patient level (dice coefficient/accuracy/sensitivity/specificity/positive and negative predictive value/ROC AUC). Patient-level optimisation was applied to increase the performance regarding predefined statistical metrics. Gradient-weighted class activation mapping (Grad-CAM++) heatmap explainability analysis highlighted image parts with statistically important regions for algorithmic decisions. Results Regarding SIJ segmentation, a dice coefficient of 0.75 was obtained in the test dataset. For slice-by-slice structural lesion detection, a sensitivity/specificity/ROC AUC of 95%/89%/0.92 and 93%/91%/0.91 were obtained in the test dataset for erosion and ankylosis detection, respectively. For patient-level lesion detection after pipeline optimisation for predefined statistical metrics, a sensitivity/specificity of 95%/85% and 82%/97% were obtained for erosion and ankylosis detection, respectively. Grad-CAM++  explainability analysis highlighted cortical edges as focus for pipeline decisions. Conclusions An optimised deep learning pipeline, including an explainability analysis, detects structural lesions of sacroiliitis on pelvic CT scans with excellent statistical performance on a slice-by-slice and patient level. Clinical relevance statement An optimised deep learning pipeline, including a robust explainability analysis, detects structural lesions of sacroiliitis on pelvic CT scans with excellent statistical metrics on a slice-by-slice and patient level. Key Points • Structural lesions of sacroiliitis can be detected automatically in pelvic CT scans. • Both automatic segmentation and disease detection yield excellent statistical outcome metrics. • The algorithm takes decisions based on cortical edges, rendering an explainable solution.

The epithelial cell rests of Malassez (ERM) are essential in preventing ankylosis between the alveolar bone and the tooth (dentoalveolar ankylosis). Despite extensive research, the mechanism by which ERM cells suppress ankylosis remains uncertain; perhaps its varied population is to reason. Therefore, in this study, eighteen unique clones of ERM (CRUDE) were isolated using the single-cell limiting dilution and designated as ERM 1–18. qRT-PCR, ELISA, and western blot analyses revealed that ERM-2 and -3 had the highest and lowest amelogenin expression, respectively. Mineralization of human periodontal ligament fibroblasts (HPDLF) was reduced in vitro co-culture with CRUDE ERM, ERM-2, and -3 cells, but recovered when an anti-amelogenin antibody was introduced. Transplanted rat molars grown in ERM-2 cell supernatants produced substantially less bone than those cultured in other cell supernatants; inhibition was rescued when an anti-amelogenin antibody was added to the supernatants. Anti-Osterix antibody staining was used to confirm the development of new bones. In addition, next-generation sequencing (NGS) data were analysed to discover genes related to the distinct roles of CRUDE ERM, ERM-2, and ERM-3. According to this study, amelogenin produced by ERM cells helps to prevent dentoalveolar ankylosis and maintain periodontal ligament (PDL) space, depending on their clonal diversity.

To explore the role of YAP, a key effector of the Hippo pathway, in temporomandibular joint (TMJ) ankylosis. The temporal and spatial expression of YAP was detected via immunohistochemistry and multiplex immunohistochemistry on postoperative Days 1, 4, 7, 9, 11, 14 and 28 in a sheep model. Isolated mesenchymal stem cells (MSCs) from samples of the Day 14. The relative mRNA expression of YAP was examined before and after the osteogenic induction of MSCs. A YAP-silenced MSC model was constructed, and the effect of YAP knockdown on MSC function was examined. YAP is expressed in the nucleus of the key sites that determine the ankylosis formation, indicating that YAP is activated in a physiological state. The expression of YAP increased gradually over time. Moreover, the number of cells coexpressing of RUNX2 and YAP—with the osteogenic active zone labelled by RUNX2—tended to increase after Day 9. After the osteogenic induction of MSCs, the expression of YAP increased. After silencing YAP, the osteogenic, proliferative and migratory abilities of the MSCs were inhibited. YAP is involved in the early development of TMJ bony ankylosis. Inhibition of YAP using shRNA might be a promising way to prevent or treat TMJ ankylosis.

This study aimed to describe the clinical features of different types of traumatic temporomandibular joint (TMJ) ankylosis. Seventy-one patients with 102 ankylosed joints were retrospectively reviewed and categorized into four groups according to the grades of severity: type I, non-bony ankylosis of the joint with almost-normal joint space; type II, lateral bony ankylosis marked by a normal joint space that coexists with a radiolucent line; type III, complete bony ankylosis of the joint characterized by only a radiolucent line; and type IV, extensive bony ankylosis without any radiolucent line. The period of ankylosis, maximal mouth opening (MMO), rate of complications, and histopathological changes were compared among groups. Intergroup comparison showed significant differences in the clinical features of MMO and the incidence of complications (p < 0.05). Younger trauma patients tended to develop more severe types of ankylosis than older patients. Additionally, long post-trauma periods were related to the development of severe ankylosis. MMO was highly negatively correlated with the severity of ankylosis. Significant differences were noted among the four types of ankylosis. Younger trauma patients with long post-trauma periods tended to develop more severe TMJ ankylosis, experience more complications, and face more challenges in treatment than older patients.

Background The psychological symptoms of temporomandibular joint (TMJ) ankylosis were similar to that of depressive disorder, but there were no relevant evidences to confirm that the humans or animals with TMJ ankylosis had depressive disorder. The aim of this study was to investigate the association between TMJ ankylosis and depressive disorder in the rat model. Methods Thirty 3-week-old male Sprague–Dawley (SD) rats were used in this study. The damage of TMJ complexes and narrowed joint space were performed in the unilateral TMJ of test group to induce TMJ bony ankylosis (experimental side). The other TMJ of test group underwent a sham operation (sham side). The TMJs of control group did not undergo any operations. At 8 weeks postoperatively, behavioral tests, body weight, passive maximum mouth opening (PMMO), and TMJ morphological features were evaluated, and the hippocampuses were analyzed using western blotting and immunocytochemistry. The data was compared between the test group and control group by independent t-test, between the experimental side and sham side by paired t-test. The correlations between PMMO/area of bony fusion and duration of immobility, sucrose preference, CB1 receptor protein, mean optical density of CB1 receptor protein, and the number of BrdU-positive cell were evaluated using linear regression analysis. The level of significance was 0.05. Results In the test group, the traumatic TMJ complexes with narrowed joint space developed TMJ bony ankylosis, the area of bony mass of experimental side (21.26 mm 2 ) was larger than that of sham side (1.73 mm 2 ) ( p  < 0.001). There were significant difference with the sucrose preference (test group: 0.36, control group: 0.76, p  < 0.001), duration of immobility (test group: 127.36 s, control group: 59.41 s, p  < 0.001), body weight (test group: 156.70 g, control group: 270.06 g,  p  < 0.001), PMMO (test group: 9.98 mm, control group: 28.79 mm, p  < 0.001), CB1 receptor protein (test group: 41.00%, control group: 86.69%, p  < 0.001), mean optical density of CB1 receptor protein (test group: 29.60 a.u., control group: 54.69 a.u., p  < 0.001), and the number of BrdU-positive cell between the test group and control group (test group: 2133.71, control group: 4301.95, p  < 0.001). PMMO was negatively correlated with the duration of immobility ( r = 0.953, p  < 0.001), while the area of bony fusion was positively correlated (r = 0.961, p  < 0.001). PMMO was positively correlated with the sucrose preference, CB1 receptor protein, mean optical density of CB1 receptor protein, and the number of BrdU-positive cell ( r = 0.955, 0.955, 0.976, 0.958, p  < 0.001, all), while the area of bony fusion was negatively correlated ( r = 0.970, 0.981, 0.971, 0.958, p  < 0.001, all). Conclusions The present study verified that depressive disorder was found in the rat model of traumatic TMJ bony ankylosis. The severity of TMJ bony ankylosis correlated with the severity of depressive disorder.

Cervical total disc replacement (CTDR) aims to decrease the incidence of adjacent segment disease through motion preservation in the operated disc space. Ongoing data collection and increasing number of studies describing heterotopic ossification (HO) resulting in decreased mobility of implants, forced us to carefully evaluate our long-term clinical and morphological results of patients with CTDR. We present the first 54 consecutive patients treated with 65 ProdiscC™ prostheses during a 12-month period (2/2004–3/2005). All patients signed an informed consent and were included in prospective long-term study approved by hospital ethical committee. The 1- and 2-year follow-up analysis were available for all patients included and 4-year results for 50 patients (60 implants). Clinical (neck disability index-NDI, visual analog scale-VAS) and radiological follow-up was conducted at 1-, 2- and 4-years after the procedure. The Mehren/Suchomel modification of McAfee scale was used to classify the appearance of HO. Mean preoperative NDI was 34.5%, VAS for neck pain intensity 4.6 and VAS for arm pain intensity 5.0. At 1-, 2- and 4-year follow-up, the mean NDI was 30.7, 27.2, and 30.4, mean VAS for neck pain intensity 2.5, 2.1 and 2.9 and mean VAS for arm pain intensity pain 2.2, 1.9 and 2.3, respectively. Significant HO (grade III) was present in 45% of implants and segmental ankylosis (grade IV) in another 18% 4 years after intervention. This finding had no clinical consequences and 92% of patients would undergo the same surgery again. Our clinical results (NDI, VAS) are comparable with fusion techniques. Although, advanced non-fusion technology is used, a significant frequency of HO formation and spontaneous fusion in cervical disc replacement surgery must be anticipated during long-term follow-up.

[LANGUAGE= \"English\"] BACKGROUND: Reankylosis is a frequent pathology in patients who are operated for post-traumatic temporomandibular joint (TMJ) ankylosis. In the current practice, ankylosing spondylitis attacks are monitored with the increases in neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR). In this study, such a relation between TMJ reankylosis and increase in these ratios was evaluated.METHODS: Patients who were operated between January 2010 and December 2019 for unilateral or bilateral TMJ ankylosis were included in this study. Temporomandibular gap arthroplasty with an interpositional silicone block was performed for each patient by the same operative team. Each patient had standard physiotherapy. All ages and genders were included in the study. Due to the complete blood count differences between children and adults, 18 years of age was used as a cutoff between the groups. A need for reoperation was accepted as reankylosis. The NLR and PLR of children without and with reankylosis and adults without and with reankylosis were compared.RESULTS: Twenty-nine children and 38 adults were included in the study. Mean age of the children and adults were 10.8 and 37.3 years, respectively. Eleven children and eight adults had reankylosis. In patients with reankylosis, NLR and PLR were high significantly, regardless of age. In children, PLR was significantly higher in reankylosis patients. In adults, NLR was significantly higher in reankylosis patients.CONCLUSION: PLR and NLR may be utilized for predicting reankylosis, respectively, in children and adults who were operated for ankylosis due to TMJ fractures.[LANGUAGE= \"Turkish\"] AMAÇ: Ankiloz nüksü, travma sonrası gelişen temporomandibular eklem (TME) ankilozuna yönelik ameliyat olan hastalarda sık görülen bir so-rundur. Günümüzde, ankilozan spondilit alevlenmeleri, nötrofil (NLO) ve trombosit (TLO) lenfosit oranlarındaki artışlar ile takip edilmektedir. Bu çalışmada, TME ankiloz nüksü ve bu oranlardaki artış arasında benzer bir ilişinin olup olmadığı değerlendirildi.GEREÇ VE YÖNTEM: Ocak 2010 ile Aralık 2019 arasında tek veya çift taraflı TME ankilozu nedeniyle ameliyat edilen hastalar çalışmaya dahil edildi. Her hastaya aynı ekip tarafından temporomandibular eklem boşluk artroplastisi ve araya silikon blok yerleştirilmesi uygulandı. Her hastaya aynı fizyoterapi uygulandı. Çalışmaya çocuk ve erişkin hastalar dahil edildi ve cinsiyet ayrımı yapılmadı. Çocuk ve erişkinler arasında tam kan sayımı farkı olduğundan 18 yaş gruplar arasında sınır olarak belirlendi. Yeniden ameliyat gereksinimi ankiloz nüksü olarak kabul edildi. Ankiloz nüksü olan ve olmayan çocukların NLO ve TLO’ları karşılaştırıldı. Ankiloz nüksü olan ve olmayan erişkinlerin NLO ve TLO’ları karşılaştırıldı.BULGULAR: Çalışmaya 29 çocuk ve 38 erişkin dahil edildi. Çocukların ortalama yaşı 10.8 iken erişkinlerin ortalama yaşı 37.2’idi. On bir çocuk ve sekiz erişkinde ankiloz nüksü saptandı. Yaştan bağımsız olarak, ankiloz nüksü olan olguların NLO ve TLO’ları daha yüksekti. Çocuklarda olan nükslerde TLO anlamlı olarak yüksekken erişkinlerde NLO anlamlı olarak yüksekti.TARTIŞMA: Temporomandibular eklem kırığına bağlı gelişen ankilozların cerrahisi sonrası çocuklarda TLO ve erişkinlerde NLO kullanılarak ankiloz nüksü öngörüsü yapılabilir.

Primary molar ankylosis with infraocclusion can retard dental arch development and cause dental asymmetry. Despite its widespread prevalence, little is known about its molecular etiology and pathogenesis. To address this, RNA sequencing was used to generate transcriptomes of furcal bone from infraoccluded (n = 7) and non-infraoccluded (n = 9) primary second molars, all without succeeding biscuspids. Of the 18 529 expressed genes, 432 (2.3%) genes were differentially expressed between the two groups (false discovery rate < 0.05). Hierarchical clustering and principal component analysis showed clear separation in gene expression between infraoccluded and non-infraoccluded samples. Pathway analyses indicated that molar ankylosis is associated with the expression of genes consistent with the cellular inflammatory response and epithelial cell turnover. Independent validation using six expressed genes by immunohistochemical analysis demonstrated that the corresponding proteins are strongly expressed in the developing molar tooth germ, in particular the dental follicle and inner enamel epithelium. The descendants of these structures include the periodontal ligament, cementum, bone and epithelial rests of Malassez; tissues that are central to the ankylotic process. We therefore propose that ankylosis involves an increased inflammatory response associated with disruptions to the developmental remnants of the dental follicle and epithelial rests of Malassez.