Evaluation of temporomandibular joint morphology and morphometry in male osteoporotic patients using advanced imaging and biochemical markers: A cross-sectional study.

Osteoporosis is a condition with reduced bone mass and disrupted architecture. Osteoporosis affects the Temporomandibular disorders (TMD) by changing bone density and quality. This study aims to determine the nature and extent of temporomandibular joint (TMJ) involvement in osteoporotic patients by correlating TMJ morphological changes detected by CBCT with systemic bone health indicated by BMD T-scores from DEXA and analyzing BTMs in serum and saliva. This study was a cross-sectional study conducted from May 2021 to December 2022. It involved 50 participants divided into two groups (N=25). One group was healthy male, while the other group had osteoporosis male. Saliva and blood samples were collected, and diagnostic imaging was conducted. The prevalence of various bone changes in the condyle was examined using CBCT. Erosion was found to be the most common, followed by Flattening, Osteophyte, and Subchondral cysts. The study group had significantly higher rates of smooth condyle, erosive lesions, and osteophytes compared to the control group. Pseudocyst decreased on the right side but increased on the left side. Pain on the right side increased more in the study group, and the T score for osteoporosis was higher in the study group. Joint spaces, condyle diameter, and glenoid cavity measurements differed significantly between sick and healthy people, as shown by CBCT (P≤0.001). Only the ALP parameter in the serum showed a significant increase in the study group compared to the control group. Saliva analysis revealed higher levels of calcium, osteocalcin, and ALP in the case group compared to the control group. The results of this study showed that CBCT as a specialized technique in imaging by providing detailed images can be used to evaluate osteoporosis and be used as an accurate diagnostic tool.

Mesenchymal Stem Cell-Based Therapies for Temporomandibular Joint Repair: A Systematic Review of Preclinical Studies.

Temporomandibular disorders (TMDs) are a heterogeneous group of musculoskeletal and neuromuscular conditions involving the temporomandibular joint (TMJ), masticatory muscles, and associated structures. Mesenchymal stromal/stem cells (MSCs) have emerged as a promising therapy for TMJ repair. This systematic review aims to consolidate findings from the preclinical animal studies evaluating MSC-based therapies, including MSCs, their secretome, and extracellular vesicles (EVs), for the treatment of TMJ cartilage/osteochondral defects and osteoarthritis (OA). Following the PRISMA guidelines, PubMed, Embase, Scopus, and Cochrane Library databases were searched for relevant studies. A total of 23 studies involving 125 mice, 149 rats, 470 rabbits, and 74 goats were identified. Compliance with the ARRIVE guidelines was evaluated for quality assessment, while the SYRCLE risk of bias tool was used to assess the risk of bias for the studies. Generally, MSC-based therapies demonstrated efficacy in TMJ repair across animal models of TMJ defects and OA. In most studies, animals treated with MSCs, their derived secretome, or EVs displayed improved morphological, histological, molecular, and behavioral pain outcomes, coupled with positive effects on cellular proliferation, migration, and matrix synthesis, as well as immunomodulation. However, unclear risk in bias and incomplete reporting highlight the need for standardized outcome measurements and reporting in future investigations.

Loss of ß-arrestin2 aggravated condylar cartilage degeneration at the early stage of temporomandibular joint osteoarthritis.

OBJECTIVE: Temporomandibular joint osteoarthritis (TMJOA) is a chronic degenerative joint disorder characterized by extracellular matrix degeneration and inflammatory response of condylar cartilage. ß-arrestin2 is an important regulator of inflammation response, while its role in TMJOA remains unknown. The objective of this study was to investigate the role of ß-arrestin2 in the development of TMJOA at the early stage and the underlying mechanism. METHODS: A unilateral anterior crossbite (UAC) model was established on eight-week-old wild-type (WT) and ß-arrestin2 deficiency mice to simulate the progression of TMJOA. Hematoxylin-eosin (HE) staining and microcomputed tomography (micro-CT) analysis were used for histological and radiographic assessment. Immunohistochemistry was performed to detect the expression of inflammatory and degradative cytokines, as well as autophagy related factors. Terminal-deoxynucleotidyl transferase mediated nick end labeling (TUNEL) assay was carried out to assess chondrocyte apoptosis. RESULTS: The loss of ß-arrestin2 aggravated cartilage degeneration and subchondral bone destruction in the model of TMJOA at the early stage. Furthermore, in UAC groups, the expressions of degradative (Col-X) and inflammatory (TNF-α and IL-1ß) factors in condylar cartilage were increased in ß-arrestin2 null mice compared with WT mice. Moreover, the loss of ß-arrestin2 promoted apoptosis and autophagic process of chondrocytes at the early stage of TMJOA. CONCLUSION: In conclusion, we demonstrated for the first time that ß-arrestin2 plays a protective role in the development of TMJOA at the early stage, probably by inhibiting apoptosis and autophagic process of chondrocytes. Therefore, ß-arrestin2 might be a potential therapeutic target for TMJOA, providing a new insight for the treatment of TMJOA at the early stage.

YAP promotes the early development of temporomandibular joint bony ankylosis by regulating mesenchymal stem cell function.

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.

Excessive load promotes temporomandibular joint chondrocyte apoptosis via Piezo1/endoplasmic reticulum stress pathway.

Excessive load on the temporomandibular joint (TMJ) is a significant factor in the development of TMJ osteoarthritis, contributing to cartilage degeneration. The specific mechanism through which excessive load induces TMJ osteoarthritis is not fully understood; however, mechanically-activated (MA) ion channels play a crucial role. Among these channels, Piezo1 has been identified as a mediator of chondrocyte catabolic responses and is markedly increased in osteoarthritis. Our observations indicate that, under excessive load conditions, endoplasmic reticulum stress in chondrocytes results in apoptosis of the TMJ chondrocytes. Importantly, using the Piezo1 inhibitor GsMTx4 demonstrates its potential to alleviate this condition. Furthermore, Piezo1 mediates endoplasmic reticulum stress in chondrocytes by inducing calcium ion influx. Our research substantiates the role of Piezo1 as a pivotal ion channel in mediating chondrocyte overload. It elucidates the link between excessive load, cell apoptosis, and calcium ion influx through Piezo1. The findings underscore Piezo1 as a key player in the pathogenesis of TMJ osteoarthritis, shedding light on potential therapeutic interventions for this condition.

Correlation between bilateral TMJ MRI findings: A systematic review of the literature.

The correlation between magnetic resonance imaging (MRI) signs and clinical findings has been highlighted in multiple studies. However, very little information is available on the correlation between the bilateral temporomandibular joints (TMJs) of the same individual. The majority of efforts in the clinical research setting have focused on the correlation between ipsilateral imaging and clinical findings, while less attention has been paid to the contralateral imaging findings of the anatomical structures.The objective of this paper was to review the existing literature that compares temporomandibular joint (TMJ) magnetic resonance imaging (MRI) findings from both sides of the same individual.In January 2024, a systematic search of the literature from major search engines (MEDLINE (PubMed), Scopus) was conducted to identify all peer-reviewed English-language studies that presented an MRI comparison of left and right TMJ data in the same patients. The articles were analyzed using a Population/ Intervention/Comparison/Outcome (PICO) format.The search terms "temporomandibular joint" AND "magnetic" AND "resonance" yielded 2,561 results. Only 2 papers met the established inclusion criteria. The results of the papers included in the systematic review were not comparable due to differences in the evaluation of the TMJs, which prevented a meta-analysis. Manfredini et al. identified a statistical correlation between disc displacement, osseous changes (OC) and joint effusion (JE) between the joints of the contralateral sides. Koca et al. observed a significant difference in TMJ MRI findings between the painful and non-painful sides of each individual in a bruxism group and a control group (p = 0.001, p < 0.001 and p = 0.004, p < 0.001, respectively).The studies on the correlation between the right and left TMJs remain scarce. A comparative analysis of the 2 sides of the TMJ in individual patients is rarely reported.The review did not identify a common result for the findings of the contralateral TMJs in the 2 articles included.

Inflammation Triggers Chondrocyte Ferroptosis in TMJOA via HIF-1α/TFRC.

Inflammation and loss of articular cartilage are considered the major cause of temporomandibular joint osteoarthritis (TMJOA), a painful condition of the temporomandibular joint (TMJ). To determine the cause of TMJ osteoarthritis in these patients, synovial fluid of TMJOA patients was compared prior to and after hyaluronic lavage, revealing substantially elevated levels of interleukin (IL) 1ß, reactive oxidative stress (ROS), and an overload of Fe3+ and Fe2+ prior to lavage, indicative of ferroptosis as a mode of chondrocyte cell death. To ask whether prolonged inflammatory conditions resulted in ferroptosis-like transformation in vitro, we subjected TMJ chondrocytes to IL-1ß treatment, resulting in a shift in messenger RNA sequencing gene ontologies related to iron homeostasis and oxidative stress-related cell death. Exposure to rat unilateral anterior crossbite conditions resulted in reduced COL2A1 expression, fewer chondrocytes, glutathione peroxidase 4 (GPX4) downregulation, and 4-hydroxynonenal (4-HNE) upregulation, an effect that was reversed after intra-articular injections of the ferroptosis inhibitor ferrostatin 1 (Fer-1). Our study demonstrated that ferroptosis conditions affected mitochondrial structure and function, while the inhibitor Fer-1 restored mitochondrial structure and the inhibition of hypoxia-inducible factor 1α (HIF-1α) or the transferrin receptor 1 (TFRC) rescued IL-1ß-induced loss of mitochondrial membrane potential. Inhibition of HIF-1α downregulated IL-1ß-induced TFRC expression, while inhibition of TFRC did not downregulate IL-1ß-induced HIF-1α expression in chondrocytes. Moreover, inhibition of HIF-1α or TFRC downregulated the IL-1ß-induced MMP13 expression in chondrocytes, while inhibition of HIF-1α or TFRC rescued IL-1ß-inhibited COL2A1 expression in chondrocytes. Furthermore, upregulation of TFRC promoted Fe2+ entry into chondrocytes, inducing the Fenton reaction and lipid peroxidation, which in turn caused ferroptosis, a disruption in chondrocyte functions, and an exacerbation of condylar cartilage degeneration. Together, these findings illustrate the far-reaching effects of chondrocyte ferroptosis in TMJOA as a mechanism causing chondrocyte death through iron overload, oxidative stress, and articular cartilage degeneration and a potential major cause of TMJOA.

Long-term haplodeficency of DSPP causes temporomandibular joint osteoarthritis in mice.

BACKGROUND: Extracellular matrix (ECM) protein malfunction or defect may lead to temporomandibular joint osteoarthritis (TMJ OA). Dentin sialophophoprotein (DSPP) is a mandibular condylar cartilage ECM protein, and its deletion impacted cell proliferation and other extracellular matrix alterations of postnatal condylar cartilage. However, it remains unclear if long-term loss of function of DSPP leads to TMJ OA. The study aimed to test the hypothesis that long-term haploinsufficiency of DSPP causes TMJ OA. MATERIALS AND METHODS: To determine whether Dspp+/- mice exhibit TMJ OA but no severe tooth defects, mandibles of wild-type (WT), Dspp+/-, and Dspp homozygous (Dspp-/-) mice were analyzed by Micro-computed tomography (micro-CT). To characterize the progression and possible mechanisms of osteoarthritic degeneration over time in Dspp+/- mice over time, condyles of Dspp+/- and WT mice were analyzed radiologically, histologically, and immunohistochemically. RESULTS: Micro-CT and histomorphometric analyses revealed that Dspp+/- and Dspp-/- mice had significantly lower subchondral bone mass, bone volume fraction, bone mineral density, and trabecular thickness compared to WT mice at 12 months. Interestingly, in contrast to Dspp-/- mice which exhibited tooth loss, Dspp+/- mice had minor tooth defects. RNA sequencing data showed that haplodeficency of DSPP affects the biological process of ossification and osteoclast differentiation. Additionally, histological analysis showed that Dspp+/- mice had condylar cartilage fissures, reduced cartilage thickness, decreased articular cell numbers and severe subchondral bone cavities, and with signs that were exaggerated with age. Radiographic data showed an increase in subchondral osteoporosis up to 18 months and osteophyte formation at 21 months. Moreover, Dspp+/- mice showed increased distribution of osteoclasts in the subchondral bone and increased expression of MMP2, IL-6, FN-1, and TLR4 in the mandibular condylar cartilage. CONCLUSIONS: Dspp+/- mice exhibit TMJ OA in a time-dependent manner, with lesions in the mandibular condyle attributed to hypomineralization of subchondral bone and breakdown of the mandibular condylar cartilage, accompanied by upregulation of inflammatory markers.

Integration of metabolomics and transcriptomics provides insights into the molecular mechanism of temporomandibular joint osteoarthritis.

The deficiency of clinically specific biomarkers has made it difficult to achieve an accurate diagnosis of temporomandibular joint osteoarthritis (TMJ-OA) and the insufficient comprehension of the pathogenesis of the pathogenesis of TMJ-OA has posed challenges in advancing therapeutic measures. The combined use of metabolomics and transcriptomics technologies presents a highly effective method for identifying vital metabolic pathways and key genes in TMJ-OA patients. In this study, an analysis of synovial fluid untargeted metabolomics of 6 TMJ-OA groups and 6 temporomandibular joint reducible anterior disc displacement (TMJ-DD) groups was conducted using liquid and gas chromatography mass spectrometry (LC/GC-MS). The differential metabolites (DMs) between TMJ-OA and TMJ-DD groups were analyzed through multivariate analysis. Meanwhile, a transcriptomic dataset (GSE205389) was obtained from the GEO database to analyze the differential metabolism-related genes (DE-MTGs) between TMJ-OA and TMJ-DD groups. Finally, an integrated analysis of DMs and DE-MTGs was carried out to investigate the molecular mechanisms associated with TMJ-OA. The analysis revealed significant differences in the levels of 46 DMs between TMJ-OA and TMJ-DD groups, of which 3 metabolites (L-carnitine, taurine, and adenosine) were identified as potential biomarkers for TMJ-OA. Collectively, differential expression analysis identified 20 DE-MTGs. Furthermore, the integration of metabolomics and transcriptomics analysis revealed that the tricarboxylic acid (TCA) cycle, alanine, aspartate and glutamate metabolism, ferroptosis were significantly enriched. This study provides valuable insights into the metabolic abnormalities and associated pathogenic mechanisms, improving our understanding of TMJOA etiopathogenesis and facilitating potential target screening for therapeutic intervention.

A study on volumetric change of mandibular condyles with osteoarthritis using cone-beam computed tomography.

This study aimed to quantitatively assess three-dimensional changes in the mandibular condyle with osteoarthritis using cone-beam computed tomography (CBCT). Pre- and post-treatment CBCT images of temporomandibular joints (TMJs) from 66 patients were used to assess longitudinal changes in condylar volume within individual patients using 3D slicer software. Total volume difference (dV), net increase (dV + , bone deposition), and net decrease (dV- , bone resorption) after treatment were analyzed based on clinical and radiological factors. Condyles with surface erosion at their first visit showed significantly decreased volume after treatment compared to condyles without erosion (p < 0.05). Amounts of bone resorption and deposition were higher in condyles with surface erosion (both p < 0.01). In patients with condylar erosion, the presence of joint pain was associated with a decrease in condylar volume and an increase in net resorption (both p < 0.01). When both joint pain and condylar erosion were present, patients with parafunctional habits showed reduced condylar volume after treatment (p < 0.05). Condylar volume change after treatment was negatively correlated with the duration of pain relief (R = - 0.501, p < 0.05). These results indicate that condylar erosion and TMJ pain could be significant variables affecting TMJ volume changes after treatment. Establishing appropriate treatment strategies is crucial for managing condylar erosion and TMJ pain.

[Imaging in temporomandibular joint disorders]. / Beeldvorming bij kaakgewrichtsstoornissen.

The temporomandibular joint is a unique and complex joint. Various imaging techniques have been developed to properly visualize this complex joint, such as conventional radiology, orthopantomography, CBCT and MRI. Imaging can contribute to the differential diagnosis of temporomandibular joint disorders. Common joint disorders are arthritis and internal derangement. Osseous changes of the temporomandibular joint can be clearly visualized with CBCT. MRI is superior for imaging the internal anatomy of the temporomandibular joint and is preferred in the context of internal derangement.

A Three-branch Jointed Feature and Topology Decoder guided by game-theoretic interactions for temporomandibular joint segmentation.

Segmentation of the temporomandibular joint (TMJ) disc and condyle from magnetic resonance imaging (MRI) is a crucial task in TMJ internal derangement research. The automatic segmentation of the disc structure presents challenges due to its intricate and variable shapes, low contrast, and unclear boundaries. Existing TMJ segmentation methods often overlook spatial and channel information in features and neglect overall topological considerations, with few studies exploring the interaction between segmentation and topology preservation. To address these challenges, we propose a Three-Branch Jointed Feature and Topology Decoder (TFTD) for the segmentation of TMJ disc and condyle in MRI. This structure effectively preserves the topological information of the disc structure and enhances features. We introduce a cross-dimensional spatial and channel attention mechanism (SCIA) to enhance features. This mechanism captures spatial, channel, and cross-dimensional information of the decoded features, leading to improved segmentation performance. Moreover, we explore the interaction between topology preservation and segmentation from the perspective of game theory. Based on this interaction, we design the Joint Loss Function (JLF) to fully leverage the features of segmentation, topology preservation, and joint interaction branches. Results on the TMJ MRI dataset demonstrate the superior performance of our TFTD compared to existing methods.

Effect of the application of digital technology-assisted optimization in the process of adjusting jaw position.

OBJECTIVES: The aim of this study was to demonstrate a novel jaw position adjustment technique derived from digital twins and evaluate the application effect of digital technology-assisted optimization in the process of adjusting jaw position on patients with temporomandibular disorders (TMD). METHODS: A total of 74 patients with TMD who attended the Department of Temporomandibular Joint, West China Hospital of Stomatology, Si-chuan University, between June 2022 and May 2023 were selected. The patient's initial computed tomography (CT) and bilateral temporomandibular joint data obtained by magnetic resonance imaging (MRI) were collected. The 148 joints were divided into the normal disc-condyle relationship (N) group, disc displacement with reduction (DDWR) group, and disc displacement without reduction (DDWoR) group. Assisted by digital technology, the patient's CT data were reconstructed, and a personalized reference plane was established to adjust the jaw position. A three-point bite guiding splint was designed by the adjusted occlusal space and then fabricated by 3D printing technology. It was worn by the patients and then reviewed by MRI. Before and after the adjustment of jaw position, the amount and direction of condyle and disc displacement and the angle between condyle and disc were measured as the evaluation indexes of the effect of the adjustment. The correlation with condylar displacement was evaluated. RESULTS: In the N group, the disc moved backward and downward along the X and Z axes by (-0.60±0.62) and (0.51±0.71) mm, respectively. In the DDWR group, the disc moved backward and upward along the X and Z axes by (-1.33±1.38) and (-0.09±1.31) mm, respectively. In the DDWoR group, the disc moved forward and downward along the X and Z axes by (0.49±1.76) and (1.35±1.76) mm, respectively. The angle between the condyle and the disc decreased after adjustment of the jaw position in all three groups. All patients showed improvement in symptoms after adjustment. CONCLUSIONS: Digital technology-assisted jaw position adjustment can simplify the process, reduce the sensitivity of the technique, and improve patients' disc-condyle structure and symptoms. Therefore, its application in the treatment of patients with TMD is of great clinical significance.

Glutathione peroxidase 4 restrains temporomandibular joint osteoarthritis progression by inhibiting ferroptosis.

There are few effective therapeutic strategies for temporomandibular joint osteoarthritis (TMJOA) due to the unclear pathology and mechanisms. We aimed to confirm the roles of GPX4 and ferroptosis in TMJOA progression. ELISA assay was hired to evaluate concentrations of ferroptosis-related markers. The qRT-PCR assay was hired to assess gene mRNA level. Western blot assay and immunohistochemistry were hired to verify the protein level. CCK-8 assay was hired to detect cell viability. Human fibroblast-like synoviocytes (FLSs) were cultured to confirm the effects of GPX4 and indicated inhibitors, and further verified the effects of GPX4 and ferroptosis inhibitors in TMJOA model rats. Markers of ferroptosis including 8-hidroxy-2-deoxyguanosine (8-OHdG) and iron were notably increased in TMJOA tissues and primary OA-FLSs. However, the activity of the antioxidant system including the glutathione peroxidase activity, glutathione (GSH) contents, and glutathione/oxidized glutathione (GSH/GSSG) ratio was notably inhibited in TMJOA tissues, and the primary OA-FLSs. Furthermore, the glutathione peroxidase 4 (GPX4) expression was down-regulated in TMJOA tissues and primary OA-FLSs. Animal and cell experiments have shown that ferroptosis inhibitors notably inhibited ferroptosis and promoted HLS survival as well as up-regulated GPX4 expression. Also, GPX4 knockdown promoted ferroptosis and GPX4 overexpression inhibited ferroptosis. GPX4 also positively regulated cell survival which was the opposite with ferroptosis. In conclusion, GPX4 and ferroptosis regulated the progression of TMJOA. Targeting ferroptosis might be an effective therapeutic strategy for TMJOA patients in the clinic.

The short- and long-term effects of congenital occlusion loss of the unilateral first permanent molar on the temporomandibular joint morphology and position: A retrospective study based on cone-beam computed tomography.

OBJECTIVE: To investigate the effects of congenital unilateral first permanent molar occlusal loss (CUMOL) on the morphology and position of temporomandibular joint (TMJ). MATERIALS AND METHODS: Cone-beam computed tomography (CBCT) images of 37 patients with CUMOL (18 males and 19 females, mean age: 13.60 ± 4.38 years) were divided into two subgroups according to the status of second molar (G1: the second molar not erupted, n = 18, G2: second molar erupted, n = 19). The control group consisted of 33 normal occlusion patients (9 males and 24 females, mean age: 16.15 ± 5.44 years) and was divided into 2 subgroups accordingly (G3: the second molar had not erupted, n = 18, G4: the second molar had erupted and made contact with the opposing tooth, n = 15). Linear and angular measurements were used to determine the characteristics of TMJ. RESULTS: In G1, the condyle on the side of the CUMOL shifts posteriorly, with significant side differences observed in Anterior space (AS, P < .05) and Posterior space (PS, P < .05). However, with the eruption of the second permanent molars, in G2, the condyle on the CUMOL side moves posteriorly and inferiorly. This results in significant lateral differences in the AS (P < .05), PS (P < .05), and Superior space (SS, P < .05). Additionally, there is an increase in the thickness of the roof of the glenoid fossa (TRF) on the CUMOL side (P < .05), and a decrease in the inclination of the bilateral articular eminences (P < .05). CONCLUSIONS: CUMOL can affect the position and the morphology of the condyle and was associated with the eruption of the second permanent molars. Before the eruption of the second permanent molars, CUMOL primarily affects the position of the condyle. After the emergence of the second permanent molars, CUMOL leads to changes in both the condyle's position and the morphology of the glenoid fossa.

Metabolic profiling of synovial fluid in human temporomandibular joint osteoarthritis.

Introduction: Temporomandibular joint (TMJ) osteoarthritis (OA) is a common TMJ degenerative disease with an unclear mechanism. Synovial fluid (SF), an important component of TMJ, contains various proteins and metabolites that may directly contribute to OA. The present study aimed to investigate the influence of SF in TMJOA at the metabolite level. Methods: Untargeted and widely targeted metabolic profiling were employed to identify metabolic changes in SF of 90 patients with different TMJOA grades according to TMJ magnetic resonance imaging. Results: A total 1498 metabolites were detected. Most of the metabolites were amino acids and associated metabolites, benzene and substituted derivatives, and lipids. Among patients with mild, moderate and severe TMJOA, 164 gradually increasing and 176 gradually decreasing metabolites were identified, indicating that biosynthesis of cofactors, choline metabolism, mineral absorption and selenocompound metabolism are closely related to TMJOA grade. Combined metabolomics and clinical examination revealed 37 upregulated metabolites and 16 downregulated metabolites in patients with pain, of which 19 and 26 metabolites were positively and negatively correlated, respectively, with maximum interincisal opening. A model was constructed to diagnose TMJOA grade and nine biomarkers were identified. The identified metabolites are key to exploring the mechanism of TMJOA. Discussion: In the present study, a metabolic profile was constructed and assessed using a much larger number of human SF samples from patients with TMJOA, and a model was established to contribute to the diagnosis of TMJOA grade. The findings expand our knowledge of metabolites in human SF of TMJOA patients, and provide an important basis for further research on the pathogenesis and treatment of TMJOA.

The relationship of ALPK1, hyaluronic acid and M1 macrophage polarization in the temporomandibular joint synovitis.

M1 macrophage polarization and synovitis play an important role in the pathogenesis of temporomandibular joint osteoarthritis (TMJOA). Reduced molecular weight of hyaluronic acid (HA) in synovial fluid of patients with TMJOA. In addition, high molecular weight hyaluronic acid (HMW-HA) is often used clinically to treat TMJ inflammation. As a pattern recognition receptor of the cytoplasm, ALPK1 was found to be pro-inflammatory in a variety of diseases. However, the relationship of ALPK1, HA and M1 macrophage polarization in TMJ synovitis remains unclear. We aimed to investigate the role of ALPK1 and HA in macrophage polarization and TMJ synovitis and the underlying mechanisms. The results demonstrated that ALPK1 was highly upregulated in the synovial macrophages in the inflamed TMJ synovium of patients. Low molecular weight hyaluronic acid (LMW-HA) promoted the expression of ALPK1 and M1 macrophage-associated genes. Besides, rhALPK1 promoted the expression of M1 macrophage-associated factors and the nuclear translocation of PKM2. Furthermore, ALPK1 knockout mice exhibited limited infiltration of macrophages and decreased expression levels of M1 macrophage-associated genes in CFA-induced TMJ synovitis. While HMW-HA inhibited the expression of ALPK1 and M1 macrophage polarization. Our results elucidated that ALPK1 promoted TMJ synovitis by promoting nuclear PKM2-mediated M1 macrophage polarization, whereas HMW-HA inhibited the expression of ALPK1 as well as M1 macrophage polarization.

Analysis of clinical changes and magnetic resonance imaging features of 37 patients with temporomandibular joint disc condylar complex with anterior disc displacement without reduction.

OBJECTIVES: This study aims to investigate clinical outcomes, imaging changes, and age differences with regard to temporomandibular joint disc condylar complex with anterior disc displacement without reduction (ADDWoR). METHODS: A total of 37 patients (45 lateral joints) with ADDWoR who were admitted to The First Affiliated Hospital of Zheng Zhou University from January 2016 to June 2023 were selected. The patients were composed of 4 males and 33 females and had an average age of 23.5 years. The average course of the disease was 14.4 months. Clinical and magnetic resonance imaging (MRI) data were collected at the end of initial diagnosis and follow-up, and the length and thickness of the articular disc, the angle of the disc condyle, and the height of the condyle were measured. The statistical significance of the changes was assessed using SPSS 25.0 software package. RESULTS: At the end of follow-up, disc displacement in three patients (three lateral joints) was healed. Approximately 48.4% of the patients felt that limitation of mandibular movement was not alleviated; 58.3% of patients reported that pain during mouth opening was not reduced; 54.5% reported pain while chewing; 33.3% of the patients showed facial deviation, and only one showed remission. The mean disk-condyle angle increased from 61.63° to 67.81°. The average length of articular disc shortened from 8.20 mm to 7.27 mm, and the height of the condyle significantly decreased from 23.17 mm to 22.76 mm (P<0.05). The absorption ratio of the condyle increased, and no significant differences in the changes of joint soft and hard tissues between the adolescent and adult groups (P>0.05). CONCLUSIONS: In different age groups of patients with ADDWoR, clinical symptoms cannot be completely relieved. The disc is anteriorly displaced and shortens, condylar height decreases, and secondary facial asymmetry and mandibular retraction occur.

[Recent research advances of angiogenesis in temporomandibular joint osteoarthritis].

Temporomandibular joint osteoarthritis (TMJOA) is a degenerative disease of temporomandibular joint, which has a high incidence and affects the quality of patients' life. While the pathogenesis of TMJOA remains unclear. It has been found that angiogenesis is involved in the development of TMJOA and it is closely related to the degradation of articular cartilage matrix, subchondral ossification, osteophyte formation and pain. This article reviews the recent advances in the study of angiogenesis in TMJOA, and provides a prospect for the treatment of TMJOA.

miR-708-5p deficiency involves the degeneration of mandibular condylar chondrocytes via the TLR4/NF-κB pathway.

OBJECTIVE: Ageing and aberrant biomechanical stimulation are two major risk factors for osteoarthritis (OA). One of the main characteristics of aged cartilage is cellular senescence. One of the main characteristics of osteoarthritic joints is cartilage degeneration. The cells in the temporomandibular joint (TMJ) cartilage are zonally arranged. The deep zone cells are differentiated from the superficial zone cells (SZCs). The purpose of the present study was to investigate whether degenerative shear stress (SS) stimulates the senescence programme in TMJ SZCs, and to determine which miRNA is involved in this process. METHOD: SZCs were isolated from the TMJ condyles of 3-week-old rats and treated with continuous passaging or SS. RNA sequencing was conducted to identify miRNA(s) that overlap with those involved in the replication senescence process and the SS-induced degeneration programme. Unilateral anterior crossbite (UAC), which is TMJ-OA inducible, was applied to 2-month-old and 12-month-old mice for 3 weeks. The effect of TMJ local injection of agomiR-708-5p was evaluated histologically. RESULTS: Both replication and SS treatment induced SZC senescence. miR-708-5p was identified. Knocking down miR-708-5p in SS-treated SZCs led to more severe senescence by alleviating the inhibitory impact of miR-708-5p on the TLR4/NF-κB pathway. miR-708-5p expression in mouse TMJ cartilage decreased with age. UAC induced more severe osteoarthritic cartilage lesions in 12-month-old mice than in 2-month-old mice. Injection of agomiR-708-5p suppressed UAC-induced osteoarthritic cartilage lesions. CONCLUSIONS: Age-related miR-708-5p deficiency is involved in the mechanically stimulated OA process. Intra-articular administration of agomiR-708-5p is a promising new strategy for OA treatment.