Temporomandibular Joint Osteoarthritis Research Articles

AI and radiologist assessments on the prevalence of TMJ osteoarthritis using radiographic images: A comparative study

Objectives: This study aims to address the significant discomfort and functional impairment associated with temporomandibular joint osteoarthritis (TMJ OA), which negatively impacts the quality of life. It emphasizes the importance of prompt diagnosis and explores the potential of an Artificial Intelligence (AI) system to enhance TMJ OA diagnosis. Methods: The prevalence of TMJ OA was evaluated using 3 diagnostic tools: the gold standard, the AI model, and an examiner. In total, 132 patients who performed 190 cone-beam computed tomography (CBCT) images were included. Results: The prevalence of TMJ OA was 62.11% using the gold standard, 63.68% using the AI model, and 58.42% when assessed by the examiner. No gender variation in TMJ OA diagnosis was reported (p-value>0.05). Age variations were reported with the gold standard and the examiner diagnosis. When compared to the gold standard, the AI model had remarkable sensitivity (97.46%) and specificity (91.67%). Conclusions: The AI model shows promise in enhancing the accuracy of TMJ OA diagnosis, offering potential benefits for early detection and improved patient outcomes.

FTO in oral diseases: Functions, mechanisms, and therapeutic potential.

Fat mass and obesity-associated protein (FTO) is the first identified N6-methyladenosine (m6A) demethylase widely distributed in various tissues in adults and children. It plays an essential role in diverse mRNA-associated processes including transcriptional stability, selective splicing, mRNA translocation, and also protein translation. Recently, emerging studies have shown that FTO is involved in the genesis and development of oral diseases. However, the correlation between FTO and oral diseases and its specific regulatory mechanism still needs further study. In this review, we will summarize the discovery, distribution, gene expression, protein structure, biological functions, inhibitors, and quantifying methods of FTO, as well as its regulatory role and mechanism in oral diseases. Notably, FTO genetic variants are strongly associated with periodontal diseases (PDs), temporomandibular joint osteoarthritis (TMJOA), and obstructive sleep apnea (OSA). Besides, the latest studies that describe the relationship between FTO and PDs, head and neck squamous cell carcinoma (HNSCCs), TMJOA, and OSA will be discussed. We elaborate on the regulatory roles of FTO in PDs, HNSCCs, and TMJOA, which are modulated through cell proliferation, cell migration, apoptosis, bone metabolism, and immune response. The review will enrich our understanding of RNA epigenetic modifications in oral diseases and present a solid theoretical foundation for FTO to serve as a novel diagnosis and prognostic biomarker for oral diseases.

Identification of potential immune-related genes and infiltrations in temporomandibular joint osteoarthritis

Objective: The aim of this study was to investigate the potential inflammatory cytokines and chemokines markers for temporomandibular joint osteoarthritis (TMJOA) diagnosis using a bioinformatics analysis. Methods: The differentially expressed genes of mRNA (DEGs) and transcripts of lncRNA (DETs) were identified between TMJOA samples and normal controls curated from GSE205389 by the “DESeq. 2” R package. KEGG and GO were conducted using the R package “ggplot2” and “clusterProfiler”. A PPI network was constructed to identify hub genes by using the STRING and Cytoscape. The co-expression network was constructed between mRNA and lncRNA to check the potential regulation and function of lncRNA on protein coding genes. Finally, the immune cell infiltration analysis was conducted with CIBERSORTx and confirmed with xCells. Results: We identified 171 DEGs and DETs, of which the DEGs were closely related to immune response, T cell activation, cytokine-cytokine-receptor interaction, and the muscle system process. PPI network of the DEGs screened the top 10 hub genes, including IL6, IL1B, IL10, CCL2, CCL5, CXCL1, CXCL10, ICAM1, CSF1 and MMP1. Additionally, the immune cell infiltration analysis showed that CD8+ T cells, M1 macrophage and B cells infiltration were increased in TMJOA samples. Finally, we demonstrated that the co-expression between mRNA and lncRNA was mainly enriched in inflammatory and muscle related pathways. Conclusions: We found that immune and muscle system related pathways as well as the immune infiltration played a significant role in the TMJOA development. Additionally, inflammatory cytokines and chemokines could be crucial markers for early-stage TMJOA diagnosis and personalized treatment strategies.

β-catenin Orchestrates Gli1+ Cell Fate in Condylar Development and TMJOA.

The fibrocartilage stem cells (FCSCs) on the surface of the condyle play an essential role in cartilage homeostasis and regeneration. However, few well-defined stem cell markers have been identified for the analysis of FCSCs' cell fate and regulation mechanism. In this study, we first mapped the transcriptional landscape of the condylar cartilage and identified a Gli1+ subset. Label-retaining cells and our lineage-tracing study showed that Gli1 labeled a group of FCSCs. Conditional knockout β-catenin inhibited Gli1+ cells differentiating into hypertrophic chondrocytes. In discectomy-induced temporomandibular joint osteoarthritis (TMJOA), Gli1+ cells were further activated, and their differentiation into hypertrophic chondrocytes was accelerated, which induced stem cell pool depletion. The deletion of β-catenin in Gli1+ cells preserved the FCSC pool and alleviated TMJOA cartilage degeneration. Collectively, we uncovered that a Gli1+ FCSC subpopulation and Wnt/β-catenin signaling orchestrate the Gli1+ cell fate in condyle postnatal development and TMJOA.

Adipose tissue-derived extracellular vesicles aggravate temporomandibular joint osteoarthritis associated with obesity.

Temporomandibular joint osteoarthritis (TMJ OA) is a major disease that affects maxillofacial health and is characterised by cartilage degeneration and subchondral bone remodelling. Obesity is associated with the exacerbation of pathological manifestations of TMJ OA. However, the underlying mechanism between adipose tissue and the TMJ axis remains limited. To evaluate the effects of obesity and the adipose tissue on the development of TMJ OA. The obesity-related metabolic changes in TMJ OA patients were detected by physical signs and plasma metabolites. The effects of adipose tissue-derived EVs (Ad-EVs) on TMJ OA was investigated through histological and cytological experiments as well as gene editing technology. Alterations of Ad-EVs in obese state were identified by microRNA-seq analysis and the mechanism by which EVs affect TMJ OA was explored in vitro and in vivo. Obesity and the related metabolic changes were important influencing factors for TMJ OA. Ad-EVs from obese mice induced marked chondrocyte apoptosis, cartilage matrix degradation and subchondral bone remodelling, which exacerbated the development of TMJ OA. Depletion of Ad-EVs secretion by knocking out the geranylgeranyl diphosphate synthase (Ggpps) gene in adipose tissue significantly inhibited the obesity-induced aggravation of TMJ OA. MiR-3074-5p played an important role in this process . Our work unveils an unknown link between obese adipose tissue and TMJ OA. Targeting the Ad-EVs and the miR-3074-5p may represent a promising therapeutic strategy for obesity-related TMJ OA. High-fat-diet-induced obesity aggravate the progression of TMJ OA in mice. Obese adipose tissue participates in cartilage damage through the altered miRNA in extracellular vesicles. Inhibition of miR-3074-5p/SMAD4 pathway in chondrocyte alleviated the effect of HFD-EVs on TMJ OA.

An "All-in-One" Strategy to Reconstruct Temporomandibular Joint Osteoarthritic Microenvironment Using γ-Fe2O3@TA@ALN Nanoparticles.

Current clinical strategies for the treatment of temporomandibular joint osteoarthritis (TMJOA) primarily target cartilage biology, overlooking the synergetic effect of various cells and inorganic components in shaping the arthritic microenvironment, thereby impeding the effectiveness of existing therapeutic options for TMJOA. Here, γ-Fe2O3@TA@ALN magnetic nanoparticles (γ-Fe2O3@TA@ALN MNPs) composed of γ-Fe2O3, tannic acid (TA), and alendronate sodium (ALN) are engineered to reconstruct the osteoarthritic microenvironment and mitigate TMJOA progression. γ-Fe2O3@TA@ALN MNPs can promote chondrocytes' proliferation, facilitate chondrogenesis and anisotropic organization, enhance lubrication and reduce cartilage wear, and encourage cell movement. Magnetic-responsive γ-Fe2O3@TA@ALN MNPs also exhibit pH sensitivity, which undergoes decomposition within acidic environment to release ALN on demand. Under a 0.2 T static magnetic field, γ-Fe2O3@TA@ALN MNPs accelerate the synthesis of cartilage-specific proteins, and suppress catabolic-related genes expression and reactive oxygen species generation, affording additional protection to TMJ cartilage. In TMJOA mouse models, articular injection of γ-Fe2O3@TA@ALN MNPs effectively alleviates cartilage degeneration and subchondral bone loss in short and long terms, offering promising avenues for the development of therapeutic interventions for TMJOA.

Temporomandibular Joint Pain Measurement by Bite Force and Von Frey Filament Assays in Mice.

Temporomandibular joint (TMJ) pain and osteoarthritis (OA) are common and debilitating disorders that impair patients' quality of life. The mechanisms driving diseases-related pain are poorly understood, and current treatments fail to provide effective and long-term therapeutic effects. Additionally, pain assessment in research, particularly orofacial pain, poses several challenges that complicate studies in both clinical and basic science settings. Therefore, we have established an inflammatory TMJ pain mouse model via intra-articular injection of CFA (Complete Freund's Adjuvant) and evaluated pain behaviors by bite force measurement and the von Frey filament test. Mice with CFA injection exhibited orofacial pain behaviors compared to PBS injection, including reduced bite force and head withdrawal threshold in the von Frey filament test. These methods are relatively easy to execute to have reproducible results and can be potentially extended to pain studies for other disease models related to TMJ disorders. Together, bite force, and the von Frey filament tests are reliable in measuring orofacial pain, as demonstrated in CFA injection-induced painful TMJOA mouse models.

Lipoxin A4 modulates the PKA/CREB and NF-κB signaling pathway to mitigate chondrocyte catabolism and apoptosis in temporomandibular joint osteoarthritis

Temporomandibular joint osteoarthritis (TMJ-OA) is characterized by the degradation of the extracellular matrix (ECM) in cartilage and the apoptosis of chondrocytes, which is caused by inflammation and disruptions of chondrocyte metabolism and inflammation. Lipoxin A4 (LXA4), a specialized pro-resolving mediator, has been shown to inhibit inflammation and regulate the balance between ECM synthesis and degradation. However, the therapeutic effects of LXA4 on TMJ-OA and its underlying mechanisms remain unclear. Interleukin-1 beta (IL-1β)-induced chondrocyte and surgically induced TMJ-OA rat models were established in this study. The viability of chondrocytes treated with LXA4 was evaluated with the cell counting kit-8 (CCK-8) assay, while protein levels were assessed by western blot analysis, and the apoptosis rate was evaluated with terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labelling (TUNEL) staining. Histological analysis was conducted to evaluate the impact of LXA4 on cartilage degradation in TMJ-OA rat models. In vitro, the qRT-PCR and western blot analysis demonstrated that LXA4 facilitated the upregulation of collagen proteins (Collagen II) and decreased expression of matrix metalloproteinases (MMP-3, and MMP-13) associated with ECM modulation. LXA4 enhanced the TMJ-OA chondrocyte viability and decreased apoptotic rate. In vivo, histology and immunohistochemistry (IHC) analysis revealed that intraperitoneal injection of LXA4 contributed to the amelioration of chondrocyte injuries and deceleration of TMJ-OA. Transcriptomic sequencing revealed that cAMP signaling pathway was up-regulated and NF-κB signaling pathway was down-regulated in LXA4 treated group. LXA4 inhibited the phosphorylation of P65 and inhibitor of nuclear factor kappa B (IκBα) proteins while enhancing the phosphorylation PKA and CREB. This study demonstrates the potential of LXA4 as a therapeutic agent for suppressing chondrocyte catabolism and apoptosis by increasing PKA/CREB activity and decreasing NF-κB signaling.

Microgel Encapsulated Mesoporous Silica Nanoparticles for Releasing Wnt16 to Synergistically Treat Temporomandibular Joint Osteoarthritis.

Temporomandibular joint osteoarthritis (TMJOA) is a commonly encountered degenerative joint disease in oral and maxillofacial surgery. Recent studies have shown that the excessive unbalanced activation of Wnt/β-catenin signaling is connected with the pathogenesis of TMJOA and due to the inability to inhibit the over-activated Wnt pathway, while Wnt16-deficient mice has a more severe Knee OA. However, the efficacy of direct intra-TMJ injection of Wnt16 for the relief of TMJOA is still not directly confirmed. Moreover, small-molecule drugs such as Wnt16 usually exhibit short-lived efficacy and poor treatment adherence. Therefore, in order to obtain a stable release of Wnt16 both in the short and long term, this study fabricates a double-layer slow-release Wnt16 carrier based on mesoporous silica nanospheres (MSNs) encased within hyaluronic acid (HA) hydrogels. The biofunctional hydrogel HA/Wnt16@MSN is analyzed both in vitro and in vivo to evaluate the treatment of TMJOA. As a result, it shows superior pro-cartilage matrix restoration and inhibition of osteoclastogenesis ability, and effectively inhibits the over-activation of the Wnt/β-catenin pathway. Taken together, biofunctional hydrogel HA/Wnt16@MSN is a promising candidate for the treatment of TMJOA.

Variation in Craniodental Pathologies Among Cercopithecoid Primates.

Pathologies of the skull and teeth are well documented for many human populations, but there are fewer studies of other primates. We contrast lesion prevalence and patterning among cercopithecoid primates and map variation onto socioecological variables. We compare craniodental lesions in six species: Nasalis larvatus (n = 54), Colobus polykomos (n = 64), Cercopithecus mitis (n = 65), Macaca fascicularis (n = 109), Theropithecus gelada (n = 13), and Papio anubis (n = 76). One of us (C.A.K.) evaluated each adult skull for multiple lesion types using standard criteria. We also tested for a relationship between lesion prevalence and cranial suture fusion (age proxy). We used nonparametric tests for sex and species differences as well as pathology co-occurrence in SPSS. Socioecological data come from previous studies. Sex differences in lesion prevalence were only detected in P. anubis. Within taxa, some lesion types co-occurred. In Macaca, the presence of caries was associated with several other lesion types. Pulp cavity exposure co-occurred with TMJ osteoarthritis in multiple taxa. Among taxa, male P. anubis had higher lesion prevalences, particularly related to the anterior dentition and facial trauma. Because we did not detect a relationship between suture fusion and lesion prevalence, we propose that craniodental lesions may also be influenced by socioecological variables such as group composition and ratio of fruit to leaves in the diet. Our findings suggest that pain from pulp cavity exposure and related dental infections may alter chewing biomechanics and contribute to onset of TMJ osteoarthritis in nonhuman primates, as seen in humans. Further, we suggest that higher lesion prevalence in male baboons is likely related to male-male competition. Skeletal lesion analysis provides useful insight into primate socioecology, particularly for rare or difficult-to-observe phenomena, and provides additional biological context for our own species.

Effects of Glucosamine in the Temporomandibular Joint Osteoarthritis: A Review.

Osteoarthritis in the temporomandibular joint (TMJ) is a chronic disease characterized by irreversible damage to articular surfaces, including inflammation, loss of articular cartilage, and subchondral bone alterations, which would be radiographically evident only in later stages. Symptomatic slow-acting so-called nutraceutical drugs have been proposed as a treatment for osteoarthritis in comparison to non-steroidal anti-inflammatory drugs (NSAID) because of their appreciable safety profile even in long-term intake. Glucosamine, being one among them, proved highly efficient in knee osteoarthritis. However, its application in TMJ osteoarthritis dates back only to 2001 and is still inconclusive in its efficiency even with systematic reviews, in restoring the structural and functional aspects of damaged TMJ. Glucosamine, being a natural compound and also a contributor to building the matrix of articular cartilage, can be utilized effectively for TMJ osteoarthritis as an adjunct along with other conventional treatment modalities available till now, which also have moderate prognosis in most of the clinical scenarios. This review summarizes data relating to the mechanism of osteoarthritis and its management using glucosamine formulations. The beneficial effects of glucosamine on the pathophysiology of TMJ osteoarthritis are possibly due to its contribution to hyaluronic acid regulation and in establishing a proper balance between anabolism/catabolism in the articular tissues.

Intramuscular Botulinum Toxin as an Adjunct to Arthrocentesis with Viscosupplementation in Temporomandibular Disorders: A Proof-of-Concept Case-Control Investigation.

The reduction in joint load is a potential beneficial factor in managing osteoarthritis of the temporomandibular joint (TMJ). This paper aims to compare the effectiveness of the intramuscular injection of botulinum toxin (BTX-A) as an adjunct to TMJ arthrocentesis plus viscosupplementation with arthrocentesis plus viscosupplementation alone in the management of TMJ osteoarthritis. A pilot clinical retrospective study examined TMJ osteoarthritis treatments. Patients were divided into two groups: Group A received BTX-A injections and arthrocentesis with viscosupplementation, while Group B received only arthrocentesis with viscosupplementation. The study assessed outcomes based on mouth opening (MO), pain at rest (PR), pain at mastication (PF), and masticatory efficiency (ME) at various time points (baseline (T0), 1 week (T1), 2 weeks (T2), 3 weeks (T3), and 4 weeks (T4)) up to 2 months after treatment. The study included two groups, each with five patients. Group A received five weekly sessions of arthrocentesis plus viscosupplementation and a single BTX-A injection during the first arthrocentesis appointment. Group B underwent the five-session protocol of arthrocentesis plus viscosupplementation alone. MO, PF, PR, and ME improved quickly in T2 in both groups, but the improvement was of greater importance over the following weeks and lasted longer in Group A. Arthrocentesis with viscosupplementation associated with BTX-A was found to be more effective than arthrocentesis alone in improving clinical outcomes. This suggests that patients with TMJ osteoarthritis and myofascial pain may benefit from reduced muscle tone and joint load.

Multi-class segmentation of temporomandibular joint using ensemble deep learning

Temporomandibular joint disorders are prevalent causes of orofacial discomfort. Diagnosis predominantly relies on assessing the configuration and positions of temporomandibular joint components in magnetic resonance images. The complex anatomy of the temporomandibular joint, coupled with the variability in magnetic resonance image quality, often hinders an accurate diagnosis. To surmount this challenge, we developed deep learning models tailored to the automatic segmentation of temporomandibular joint components, including the temporal bone, disc, and condyle. These models underwent rigorous training and validation utilizing a dataset of 3693 magnetic resonance images from 542 patients. Upon evaluation, our ensemble model, which combines five individual models, yielded average Dice similarity coefficients of 0.867, 0.733, 0.904, and 0.952 for the temporal bone, disc, condyle, and background class during internal testing. In the external validation, the average Dice similarity coefficients values for the temporal bone, disc, condyle, and background were 0.720, 0.604, 0.800, and 0.869, respectively. When applied in a clinical setting, these artificial intelligence-augmented tools enhanced the diagnostic accuracy of physicians, especially when discerning between temporomandibular joint anterior disc displacement and osteoarthritis. In essence, automated temporomandibular joint segmentation by our deep learning approach, stands as a promising aid in refining temporomandibular joint disorders diagnosis and treatment strategies.

Hyaluronic Acid-Based Microparticles with Lubrication and Anti-Inflammation for Alleviating Temporomandibular Joint Osteoarthritis.

The pathogenesis of temporomandibular joint osteoarthritis (TMJOA) is closely associated with mechanical friction, which leads to the up-regulation of inflammatory mediators and the degradation of articular cartilage. Injectable drug-loaded microparticles have attracted widespread interest in intra-articular treatment of TMJOA by providing lubrication and facilitating localized drug delivery. Herein, a hyaluronic acid-based microparticle is developed with excellent lubrication properties, drug loading capacity, antioxidant activity, and anti-inflammatory effect for the treatment of TMJOA. The microparticles are facilely prepared by the self-assembly of 3-aminophenylboronic acid-modified hyaluronic acid (HP) through hydrophobic interaction in an aqueous solution, which can further encapsulate diol-containing drugs through dynamic boronate ester bonds. The resulting microparticles demonstrate excellent injectability, lubrication properties, radical scavenging efficiency, and antibacterial activity. Additionally, the drug-loaded microparticles exhibit a favorable cytoprotective effect on chondrocyte cells invitro under an oxidative stress microenvironment. Invivo experiments validate that intra-articular injection of drug-loaded microparticles effectively alleviates osteoporosis-like damage, suppresses inflammatory response, and facilitates matrix regeneration in the treatment of TMJOA. The HP microparticles demonstrate excellent injectability and encapsulation capacity for diol-containing drugs, highlighting its potential as a versatile drug delivery vehicle in the intra-articular treatment of TMJOA.

A case of Melkersson-Rosenthal syndrome with temporomandibular joint osteoarthritis: multidisciplinary treatment and autoimmune etiological hypothesis

BackgroundMelkersson-Rosenthal syndrome (MRS) is a rare neuro-mucocutaneous disorder characterized by recurrent edema, facial palsies, and nerve dysfunctions often associated with the plicata tongue. Although the etiology of MRS is not well understood, there is growing evidence suggesting an autoimmune involvement.Case presentationThis paper presents a case report of a 25-year-old male with MRS as the initial symptom, followed by temporomandibular joint osteoarthritis (TMJ-OA). A comprehensive diagnosis and multidisciplinary treatment approach including surgery, local injections, and oral medication were implemented, resulting in a favorable prognosis.ConclusionsThese findings support the hypothesis that MRS is a systemic granulomatous disease caused by autoimmunity, which may also influence the occurrence and development of TMJ-OA through immune-related mechanisms. This study emphasizes the significance of systemic immune regulation in the treatment of patients with MRS and TMJ-OA comorbid conditions.

Intra-articular and intraosseous approach to temporomandibular joint-targeted injections: a cadaveric investigation.

Temporomandibular joint osteoarthritis (TMJ-OA) management is complex, and several conservative and minimally invasive protocols have been proposed. Intra-articular injections of medications directed at OA have been performed, but in some cases, these medications do not directly contact the tissue lesion sites. Here, we propose a new real-time ultrasound-guided technique to inject medications directly into the subchondral bone. Ultrasound image screening was carried out with the point-of-care Clarius L15 device. Then, with the patient's mouth closed, a stainless-steel cannula with a concentric trocar was US-guided using an in-plane approach until the perforating tip of the internal trocar touched the lateral pole of the mandibular condyle. Then, the trocar was inserted through the medullary bone, where a posterior injection was made. The technique's precision was confirmed by capturing an iodine contrast solution that imaged the medullary condyle of fresh anatomical specimens processed by computed tomography. The proposed technique was effective in accessing the mandibular condyle subchondral bone in the inferior TMJ space for the simultaneously intra-articular (IA) and intra-osseous (IO) in-plane US-guided injections. Thus, its implementation may represent an important advance in early TMJ-OA treatment. This may be a promising approach, especially in OA cases in which the cortical bone is still preserved.

Ultrasmall Cu2I2 nanoclusters trigger metabolic-epigenetic reprogramming and endogenous antioxidant systems for alleviating osteoarthritis

Temporomandibular joint (TMJ) osteoarthritis (OA) affects millions of people worldwide, characterized by imbalance metabolism, excess reactive oxygen species (ROS), aberrant epigenetic alterations and so on. Currently, analgesics and anti-inflammatory drugs are mainly used for treatment, but they only alleviate symptoms. Here, we designed a ultrasmall copper-based nanoclusters agent (copper iodide coordination, Cu2I2), which exhibited remarkable ROS-scavenging activities. And the antioxidant properties of Cu2I2 nanoclusters (Cu2I2 NCs) were achieved by activating the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. Excitingly, Cu2I2 NCs exhibited excellent metabolic-epigenetic regulation property via reprogramming energy metabolism to inhibit S-adenosylmethionine (SAM)-production metabolic pathway and contributing to the global hypomethylation mediated by Dnmt3a. Then, the expression of anti-osteoclastogenic genes was upregulated. Consistent with in vitro observations, Cu2I2 NCs efficiently alleviated subchondral bone destruction of TMJ OA in rats. Altogether, this study not only provides a novel nanoclusters agent for TMJ OA treatment that can activate endogenous antioxidant systems, but also reveals the significance and feasibility of therapeutic strategies to break the bridge between metabolic and epigenetic regulation.

Exploring the therapeutic potential of urine-derived stem cell exosomes in temporomandibular joint osteoarthritis.

Temporomandibular joint osteoarthritis (TMJOA) is a degenerative ailment that causes slow cartilage degeneration, aberrant bone remodeling, and persistent discomfort, leading to a considerable reduction in the patient's life quality. Current treatment options for TMJOA have limited efficacy. This investigation aimed to explore a potential strategy for halting or reversing the progression of TMJOA through the utilization of exosomes (EXOs) derived from urine-derived stem cells (USCs). The USC-EXOs were obtained through microfiltration and ultrafiltration techniques, followed by their characterization using particle size analysis, electron microscopy, and immunoblotting. Subsequently, an invivo model of TMJOA induced by mechanical force was established. To assess the changes in the cartilage of TMJOA treated with USC-EXOs, we performed histology analysis using hematoxylin-eosin staining, immunohistochemistry, and histological scoring. Our findings indicate that the utilization of USC-EXOs yields substantial reductions in TMJOA, while concurrently enhancing the structural integrity and smoothness of the compromised condylar cartilage surface. Additionally, USC-EXOs exhibit inhibitory effects on osteoclastogenic activity within the subchondral bone layer of the condylar cartilage, as well as attenuated apoptosis in the rat TMJ in response to mechanical injury. In conclusion, USC-EXOs hold considerable promise as a potential therapeutic intervention for TMJOA.

Can treatment with chondroitin and glucosamine sulphate prevent changes in the articular disc caused by temporomandibular joint osteoarthritis?

Chondroitin and glucosamine sulphates (CGS) are considered structure-modifying drugs and have been studied in the prevention, delay or reversal of structural morphological changes in joints caused by osteoarthritis. The aim of the present study was to investigate the action of CGS on the progression of chemically induced osteoarthritis in the temporomandibular joint (TMJ) of rabbits by evaluating the serum levels of tumour necrosis factor (TNF-α) and collagen in the articular discs. A sample of 36 male rabbits was divided into three groups: control (CG), osteoarthritis (OG) and treatment (TG). The disease was induced by intra-articular injection of sodium monoiodoacetate (10 mg/mL) in the OG and TG groups bilaterally. After 10 days, the TG animals received subcutaneous injection of chondroitin sulphates and glucosamine (7.5 mg/kg) and the OG and CG received saline solution (50 μL). Euthanasia times were subdivided into 40 and 100 days. Collagen quantification was performed by biochemical and histological analysis and for the quantification of serum levels of TNF-α, an enzyme immunoassay was used. The TG showed an increase in the collagen area of the articular disc when compared to the CG and the OG. The increase collagen concentration in the discs did not show a statistically significant difference between the groups. Post-treatment TNF-α levels were significantly lower in TG compared to OG. The results indicate that CGS treatment delayed the degeneration of the collagen in the TMJ articular disc and reduced serum TNF-α levels, indicating a preventive effect on OA progression.

17β-estradiol promotes the progression of temporomandibular joint osteoarthritis by regulating the FTO/IGF2BP1/m6A-NLRC5 axis.

Temporomandibular joint osteoarthritis (TMJOA) is a degenerative cartilage disease. 17β-estradiol (E2) aggravates the pathological process of TMJOA; however, the mechanisms of its action have not been elucidated. Thus, we investigate the influence of E2 on the cellular biological behaviors of synoviocytes and the molecular mechanisms. Primary fibroblast-like synoviocytes (FLSs) isolated from rats were treated with TNF-α to establish cell model, and phenotypes were evaluated using cell counting kit-8, EdU, Tanswell, enzyme-linked immunosorbent assay, and quantitative real-time PCR (qPCR). The underlying mechanism of E2, FTO-mediated NLRC5 m6A methylation, was assessed using microarray, methylated RNA immunoprecipitation, qPCR, and western blot. Moreover, TMJOA-like rat model was established by intra-articular injection of monosodium iodoacetate (MIA), and bone morphology and pathology were assessed using micro-CT and H&E staining. The results illustrated that E2 facilitated the proliferation, migration, invasion, and inflammation of TNF-α-treated FLSs. FTO expression was downregulated in TMJOA and was reduced by E2 in FLSs. Knockdown of FTO promoted m6A methylation of NLRC5 and enhanced NLRC5 stability by IGF2BP1 recognition. Moreover, E2 promoted TMJ pathology and condyle remodeling, and increased bone mineral density and trabecular bone volume fraction, which was rescued by NLRC5 knockdown. E2 promoted the progression of TMJOA.