Temporomandibular Joint Osteoarthritis Research Articles

The Effect of Corrective Exercise on Pain Referred to The Jaw Joint (TMJ) in Elderly Women With Upper Crossed Syndrome

Background: Upper crossed syndrome is a muscular imbalance disorder associated with various referred pains, especially jaw discomfort. Complications like temporomandibular joint (TMJ) osteoarthritis may link to forward head posture and mechanical head pains resulting from this syndrome.
 Objectives: The objective of this study was to compare the impact of corrective exercise on pain of TMJ in elderly women with upper cross syndrome.
 Methods: A total of 30 elderly women with upper crossed syndrome were enrolled at the Kahrizak Elderly Care Center and randomly assigned to either a corrective exercise group or a control group. The experiment group underwent an eight-week training program. Pain levels and neck range of motion were assessed using a pain ruler and goniometer, respectively. In order to measure neck extension, the mean difference and effect size were determined using paired t-test and Cohen’s d, respectively. Referred pain ratings were analyzed using Mann-Whitney U and Wilcoxon signed-rank tests, with effect size calculations, to further understand the intervention’s effect on pain perception.
 Results: Both groups demonstrated significant changes in referred pain perceptions (P = 0.0441) post-intervention. However, regarding neck extension, neither the control nor the experiment group exhibited statistically significant alterations in neck extension (P = 0.4309)
 Conclusions: These findings indicate that corrective exercises have a positive effect on alleviating referred pain in the jaw joint caused by muscle imbalance. Given the merits of corrective exercises as a non-pharmacological intervention, they are recommended as an effective approach for improving referred pain in the jaw.

Abnormal mechanical stress induced chondrocyte senescence by YAP loss-mediated METTL3 upregulation.

Abnormal mechanical stress is the pivotal risk factor of temporomandibular joint osteoarthritis (TMJOA). This study investigated the pathogenic mechanism by which abnormal mechanical stress induced chondrocyte senescence. Cellular senescence was investigated in the rodent model of unilateral anterior crossbite and in the chondrocytes subjected to mechanical overloading invitro. The effects of Yes-associated protein (YAP) in chondrocyte senescence and its correlation with methyltransferase-like 3 (METTL3) and N6-methyladenosine (m6A) modification were evaluated. The role of m6A modification in chondrocyte senescence was determined. The therapeutic effects of m6A inhibition in TMJOA were investigated. Senescent chondrocytes were accumulated in the mechanically induced TMJOA lesions in rats and mechanical overloading could trigger chondrocyte senescence invitro. This mechanical stress-induced cellular senescence was revealed to be mediated by YAP deficiency that promoted METTL3-dependent m6A modification. Moreover, inhibition of m6A modification rescued chondrocyte senescence invitro and invivo, and suppressed TMJOA progression in rats. This study uncovered the underlying mechanism of mechanically induced senescence in TMJOA from the perspective of epitranscriptomics and revealed the therapeutic potential of m6A inhibition in TMJOA.

Multidisciplinary Rehabilitation after Hyaluronic Acid Injections for Elderly with Knee, Hip, Shoulder, and Temporomandibular Joint Osteoarthritis.

Osteoarthritis (OA) is a prevalent degenerative joint condition characterized by cartilage deterioration, joint inflammation, and functional limitations, particularly impacting the elderly population. Rehabilitation and hyaluronic acid (HA) injections are common therapeutic approaches routinely used in clinical practice, but their synergistic potential is far from being fully characterized. Thus, the aim of this narrative review was to elucidate the multilevel benefits and synergies of integrating these two approaches in multidisciplinary OA rehabilitation. This narrative review follows the scale for the assessment of narrative review articles (SANRA) criteria and involves a comprehensive literature search from July to August 2023. Two independent reviewers screened studies, including those involving human subjects with OA, rehabilitation strategies, and outcomes following HA injection, published in English. Results: HA injections might improve joint biomechanics, reducing friction, absorbing shocks, and potentially regulating inflammation. Rehabilitation plays a pivotal role in strengthening muscles, increasing the range of motion, and enhancing overall function. Optimizing rehabilitation following HA injection might provide additional benefits in joint health. OA management requires a multidisciplinary approach integrating HA injections, rehabilitation, and personalized care. Challenges in patient adherence and healthcare resources currently exist, but emerging technologies offer opportunities to enhance patient engagement and monitoring optimizing sustainability and outcomes of patients with knee, hip, shoulder, and temporomandibular joint OA.

Glycyrrhizin regulates antioxidation through Nrf2 signaling pathway in rat temporomandibular joint osteoarthritis.

Regulation of redox homeostasis could reduce osteoarthritis severity and limit disease progression, while glycyrrhizin (GL) shows great antioxidant and anti-inflammatory capacity. The aim of this study was to investigate the role of GL on oxidative stress and the potential regulatory mechanism in rat temporomandibular joint (TMJ) chondrocytes under oxidative stress, and investigate the effect of GL in the rat temporomandibular joint osteoarthritis (TMJOA) model. Rat TMJ chondrocytes were cultured in oxidative stress with different doses of GL. The effect of glycyrrhizin on the nuclear factor-erythroid 2-related factor 2 (Nrf2) in oxidative stress was evaluated by western blot and immunofluorescence staining. A rat model of TMJOA was treated with GL. Micro-computed tomography, histological and immunohistochemical analysis were used to assess the pathological change of TMJOA. The expression of superoxide dismutase 1 (SOD1), heme oxygenase-1 (HO-1), and peroxiredoxin 6 (PRDX6) were decreased, and intracellular Nrf2 signaling pathway was activated in chondrocytes in oxidative stress. GL upregulates the expression of antioxidants, especially PRDX6, as well as increases Nrf2 expression and nuclear translocation in rat condylar chondrocytes. Administration of GL attenuates condylar bone destruction, cartilage degeneration, and synovitis in rats TMJOA. Meanwhile, GL alleviated oxidative stress and enhanced the antioxidant capacity of TMJOA cartilage. This study suggested that GL alleviates rat TMJOA by regulating oxidative stress in condylar cartilage.

Liproxstatin-1 alleviates cartilage degradation by inhibiting chondrocyte ferroptosis in the temporomandibular joint.

Ferroptosis contributes to temporomandibular joint osteoarthritis (TMJOA) lesion development and is still poorly understood. In this study, we used different TMJOA animal models to examine whether ferroptosis was related to disease onset in TMJOA induced by monosodium iodoacetate (MIA), IL-1β, occlusion disorder (OD), and unilateral anterior crossbite (UAC). Immunohistochemical staining and Western blot analysis were used to detect ferroptosis- and cartilage degradation-related protein expression. Our results revealed reduced levels of the ferroptosis-related protein GPX4 in the cartilage layer, but the levels of ACSL4 and P53 were increased in the condyle. Injection of the ferroptosis inhibitor liproxstatin-1 (Lip-1) effectively decreased ACSL4, P53 and TRF expression. In vitro, IL-1β reduced cartilage extracellular matrix expression in mandibular condylar chondrocytes (MCCs). Lip-1 maintained the morphology and function of mitochondria and ameliorated the exacerbation of lipid peroxidation and reactive oxygen species (ROS) production induced by IL-1β. These results suggest that chondrocyte ferroptosis plays an important role in the development and progression of TMJOA. Inhibiting condylar chondrocyte ferroptosis could be a promising therapeutic strategy for TMJOA.

Dental and temporomandibular joint pathology of the red fox (Vulpes vulpes)

Skulls from 305 red foxes (Vulpes vulpes) were examined using predefined criteria to assess for the presence and severity of dental and temporomandibular joint (TMJ) pathology. Of the 305 specimens examined, 131 were male (42.9%), 103 were female (33.4%), 71 were of unknown sex (23.3%), 238 were adults (78.03%) and 67 were young adults (21.97%), with juveniles excluded from the study. Of a maximum of 12,810 possible teeth, 12,355 (96.5%) were present for examination, 72 (0.6%) were absent congenitally, 97 (0.8%) were acquired tooth loss and 280 (2.2%) were absent artefactually. Eight teeth (0.06%) in five specimens (1.6%) had abnormal tooth form and four (0.03%) supernumerary teeth were present across four (1.3%) specimens. Ten persistent deciduous teeth were present in seven (2.3%) specimens and six (0.05%) unerupted teeth were found in four (1.1%) specimens. Root number variation was present in 51 (0.4%) teeth, predominantly premolar teeth. Twenty-one (6.9%) specimens had lesions consistent with enamel hypoplasia and 42 (13.8%) showed root fenestrations in the maxillary alveolar bone. Periodontitis and attrition/abrasion were present in most specimens (56.7% and 96.1%, respectively). Three-hundred and eighty (3.1%) teeth were fractured, with the most common fracture type being root fractures. Eleven periapical lesions were found in nine (0.03%) specimens. Six-hundred and eight TMJs were evaluated and many specimens (11.5%) had evidence of low-grade TMJ osteoarthritis. Overall, these red foxes share similar dental pathology to other foxes, but had a higher prevalence of congenital tooth absence, persistent deciduous teeth, TMJ pathology and enamel hypoplasia.

Epigenetic PPARγ preservation attenuates temporomandibular joint osteoarthritis

ObjectivePrevious studies have demonstrated that PPARγ deficiency is associated with osteoarthritis in the knee joint. However, whether epigenetic PPARγ dysregulation has any effect on temporomandibular joint osteoarthritis (TMJOA) is unknown. This study aims to determine the role and mechanism of epigenetic PPARγ dysregulation in TMJOA. MethodsPartial TMJ discectomy was performed to induce TMJOA in rat. Primary condylar chondrocytes were isolated, and TNF-α-induced inflammatory condition was created in vitro. The expressions of PPARγ and DNA methyltransferase were investigated in vivo and in vitro. The association of PPARγ and DNA methylation was further studied by treating chondrocytes with DNA demethylation agent 5-Aza-2′-deoxycytidine (5Aza) and transfecting with siRNA of DNA methyltransferase (DNMT)1 and DNMT3a, and the methylation level of PPARγ promoter was evaluated by Bisulfite-sequencing PCR. The chondroprotective effects of 5Aza were explored in vitro and in vivo. ResultsPPARγ suppression and upregulated DNMT1/DNMT3a expression exist in TMJOA cartilage in vivo and primary condylar chondrocytes under TNF-α-induced inflammatory conditions in vitro. DNMT1 and DNMT3a elevation contributes to PPARγ-promoter hypermethylation in TMJ chondrocytes under TNF-α-induced inflammation conditions. DNA demethylation intervention by 5Aza protects chondrocytes from inflammation response in vitro. Mechanistically, 5Aza reversed the hypermethylation of the PPARγ promoter and subsequently resulted in PPARγ restoration and decreased expression of cartilage-catabolic factors in chondrocytes. Rat TMJOA model revealed that 5Aza, by reversing PPARγ suppression, effectively attenuated cartilage degeneration and stabilized cartilage homeostasis by balancing anabolic factor and catabolic factor expression. ConclusionEpigenetic PPARγ suppression may play a causal role in TMJOA pathogenesis, which can be alleviated by DNA demethylation with 5Aza treatment. This study provides new insights into the pathogenic mechanism and therapeutic strategy of TMJOA.

Circ-Slain2 Alleviates Cartilage Degradation and Inflammation of TMJOA

Temporomandibular joint osteoarthritis (TMJOA) is a degenerative disease with the cessation of matrix anabolism and aggravation of inflammation, which results in severe pain and impaired joint function. However, the mechanisms are not well understood. Circular RNAs (circRNAs) are reported to have various biological functions and participate in the development, diagnosis, prognosis, and treatment of different diseases. This study aimed to investigate the roles and mechanisms of circ-slain2 in TMJOA. We first established TMJOA mouse models and found circ-slain2 was lowly expressed in the cartilage of TMJOA through sequencing data. We observed that circ-slain2 is predominantly localized in the cytoplasm and downregulated in mouse condylar chondrocytes (mCCs) treated with tumor necrosis factor α (TNFα) and interferon γ (IFNγ). Micro–computed tomography and histological examination showed that intra-articular injection of circ-slain2 overexpressing adeno-associated virus could alleviate cartilage catabolism and synovial inflammation to relieve TMJOA in vivo. In addition, elevated circ-slain2 also showed anticatabolic and anti-inflammatory effects on IFNγ- and TNFα-stimulated mouse condylar chondrocytes (mCCs). Functional enrichment analysis indicated that protein processing in endoplasmic reticulum (ER) was associated with TMJOA, and further functional experiments confirmed that circ-slain2 could suppress ER stress in OA mCCs. RNA binding protein immunoprecipitation assay revealed an overt interaction between activating transcription factor 6 (ATF6) and circ-slain2. Inhibition of the expression of both ATF6 and circ-slain2 resulted in dilation of the ER and enhanced the expression of ER stress markers, whose ER stress level was higher than inhibition of ATF6 but lower than knockdown of circ-slain2 expression. Collectively, our research demonstrated that circ-slain2 could regulate ATF6 to relieve ER stress, reducing temporomandibular joint cartilage degradation and synovial inflammation. These findings provide prospects for developing novel osteoarthritis therapies based on circ-slain2 by focusing on reducing the inflammation of synovium and the imbalance between matrix synthesis and degradation.

Research progress in the pathologic mechanism of temporomandibular joint osteoarthritis

Temporomandibular joint osteoarthritis (TMJOA) is a kind of degenerative lesion in temporomandibular joint disorders. The pathogenesis of TMJOA is complex. Among them, excessive mechanical stress plays an important role, which can cause a series of pathological changes, including synovial inflammation, chondrocyte death, osteogenic and adipogenic differentiation, degradation of extracellular matrix of cartilage, angiogenesis, osteochondral interface sclerosis, subchondral bone remodeling, degeneration of articular discs, etc. In the pathogenesis of TMJOA, it involves multiple signal pathways and epigenetic regulation, which may become potential therapeutic targets of TMJOA. In this paper, the research progress on the pathologic mechanism of TMJOA in recent years is reviewed to provide a basis for finding new therapeutic targets of TMJOA.

Platelet-rich plasma therapy for temporomandibular joint osteoarthritis: A randomized controlled trial

The study aimed to compare the efficacy of platelet-rich plasma (PRP) injections for the treatment of temporomandibular joint osteoarthritis (TMJ-OA) with hyaluronic acid (HA) therapy.This randomized controlled trial included 70 patients with TMJ-OA, randomly divided into either a PRP or HA group. The pain intensity, maximum mouth opening (MMO), TMJ sound score, and proportion of crepitus were recorded and compared at baseline and at 1, 3, and 6 months.Both groups showed statistically significant improvements in pain intensity, MMO, TMJ sound, and scale scores during the 6-month follow-up period. The improvements in pain intensity during mouth opening at 1 month, MMO at 1, 3, and 6 months, TMJ sound score at 1 and 3 months, and GAD-7 score at 6 months in the PRP group were greater than in the HA group (p < 0.05). Compared with the HA group, imaging improvement in the PRP group was also higher (p < 0.05).Within the limitations of the study it seems that the application of PRP therapy in TMJ-OA is should be considered whenever possible.

Single-cell RNA sequencing reveals neurovascular-osteochondral network crosstalk during temporomandibular joint osteoarthritis: Pilot study in a human condylar cartilage

PurposeTemporomandibular joint osteoarthritis (TMJ-OA) is one of the most complex temporomandibular disorders, causing pain and dysfunction. The main pathological feature of TMJ-OA is neurovascular invasion from the subchondral bone to the condylar cartilage. This study aimed to discover the cells and genes that play an important role in the neurovascular–osteochondral network crosstalk in human TMJ-OA. Materials and methodsCondylar cartilages from patient with TMJ-OA were divided into OA group, and others from patients with benign condylar hyperplasia (CH) were used as control for further single-cell RNA-sequencing (scRNA-seq). Hematoxylin and eosin staining were performed. The cells and genes in the condylar cartilage were identified and analyzed by scRNA-seq. ResultsHistological analysis revealed blood vessel invasion and ossification in the TMJ-OA condylar cartilage. The scRNA-seq identified immune cells, endothelial cells, and chondrocytes in the TMJ-OA condylar cartilage. Macrophages, especially M1-like macrophages, contributed to the inflammation, angiogenesis, and innervation. CD31+ endothelial cells contributed to the bone mineralization. The TMJ-OA cartilage chondrocytes highly expressed genes related to inflammation, angiogenesis, innervation, and ossification. The hub genes contributing to these processes in the TMJ-OA chondrocytes included CTGF, FBN1, FN1, EGFR, and ITGA5. ConclusionOur study marks the first time scRNA-seq was used to identify the cells and genes in a human TMJ-OA condylar cartilage, and neurovascular–osteochondral network crosstalk during the human TMJ-OA process was demonstrated. Targeting the crosstalk of these processes may be a potential comprehensive and effective therapeutic strategy for human TMJ-OA.

Managing Temporomandibular Joint Osteoarthritis by Dental Stem Cell Secretome

The potential therapeutic role of the Dental Pulp Stem Cells Secretome (SECR) in a rat model of experimentally induced Temporomandibular Joint (TMJ) Osteoarthritis (OA) was evaluated. Proteomic profiling of the human SECR under specific oxygen tension (5% O2) and stimulation with Tumor Necrosis Factor-alpha (TNF-α) was performed. SECR and respective cell lysates (CL) samples were collected and subjected to SDS-PAGE, followed by LC-MS/MS analysis. The identified proteins were analyzed with Bioinformatic tools. The anti-inflammatory properties of SECR were assessed via an in vitro murine macrophages model, and were further validated in vivo, in a rat model of chemically-induced TMJ-OA by weekly recording of the head withdrawal threshold, the food intake, and the weight change, and radiographically and histologically at 4- and 8-weeks post-treatment. SECR analysis revealed the presence of 50 proteins that were enriched and/or statistically significantly upregulated compared to CL, while many of those proteins were involved in pathways related to “extracellular matrix organization” and “immune system”. SECR application in vitro led to a significant downregulation on the expression of pro-inflammatory genes (MMP-13, MMP-9, MMP-3 and MCP-1), while maintaining an increased expression of IL-10 and IL-6. SECR application in vivo had a significant positive effect on all the clinical parameters, resulting in improved food intake, weight, and pain suppression. Radiographically, SECR application had a significant positive effect on trabecular bone thickness and bone density compared to the saline-treated group. Histological analysis indicated that SECR administration reduced inflammation, enhanced ECM and subchondral bone repair and regeneration, thus alleviating TMJ degeneration.Graphical

An artificial intelligence model for the radiographic diagnosis of osteoarthritis of the temporomandibular joint

The interpretation of the signs of Temporomandibular joint (TMJ) osteoarthritis on cone-beam computed tomography (CBCT) is highly subjective that hinders the diagnostic process. The objectives of this study were to develop and test the performance of an artificial intelligence (AI) model for the diagnosis of TMJ osteoarthritis from CBCT. A total of 2737 CBCT images from 943 patients were used for the training and validation of the AI model. The model was based on a single convolutional network while object detection was achieved using a single regression model. Two experienced evaluators performed a Diagnostic Criteria for Temporomandibular Disorders (DC/TMD)-based assessment to generate a separate model-testing set of 350 images in which the concluded diagnosis was considered the golden reference. The diagnostic performance of the model was then compared to an experienced oral radiologist. The AI diagnosis showed statistically higher agreement with the golden reference compared to the radiologist. Cohen’s kappa showed statistically significant differences in the agreement between the AI and the radiologist with the golden reference for the diagnosis of all signs collectively (P = 0.0079) and for subcortical cysts (P = 0.0214). AI is expected to eliminate the subjectivity associated with the human interpretation and expedite the diagnostic process of TMJ osteoarthritis.

Bergapten exerts a chondroprotective effect in temporomandibular joint osteoarthritis by combining intestinal flora alteration and reactive oxygen species reduction

Bergapten, a furanocoumarin naturally occurring in bergamot essential oil, has been demonstrated to have the potential to alleviate osteoarthritis-related symptoms via its anti-inflammatory activity. Although its systemic bioavailability is limited, its precise mechanisms of action and effects on temporomandibular joint osteoarthritis (TMJOA) and its relationship with the intestinal flora remain unclear. Here, we explored the anti-TMJOA effect of BGT combined with the interleukin-1β-induced inflammatory response of chondrocytes in a monosodium iodoacetate (MIA)-induced TMJOA rat model. It was confirmed that BGT effectively reduced proinflammatory mediators and increased type II collagen, bone volume, and trabecular number of condyles in TMJOA rats. Importantly, the oral administration of BGT altered the intestinal flora of rats by increasing the relative abundances of nine prebiotic species and decreasing the relative abundance of one potential species. In addition, BGT considerably reduced reactive oxygen species (ROS) levels by suppressing glutathione, oxidized glutathione, and superoxide dismutase in the serum and malondialdehyde in urine. These results suggest that BGT exerts a chondroprotective effect, most likely by improving the intestinal flora and reducing ROS production associated with TMJOA in rats. This finding indicates a novel beneficial effect of BGT on the prevention and treatment of TMJOA.

Bone marrow aspirate concentrate – A novel approach to alter the course of temporomandibular joint osteoarthritis (a clinical study)

IntroductionTMJ OA is characterized by severe osteocartilaginous degradation of the joint structure resulting in severe deterioration of both joint function as well as joint structure. bone marrow aspirate concentrate (BMAC) gained wide acceptance as an auspicious addition for regenerative medicine as it is confirmed to be a rich source of pluripotent mesenchymal stem cells and growth factors that produce promising relief of clinical symptoms with significant repair of the joint structure. Thus, the study aims at assessing the efficacy of bone marrow aspirate concentrate (BMAC) as a treatment modality for TMJ osteoarthritis and compare its efficacy with that of hyaluronic acid (HA). Methods24 patients were included in the present study and divided into 12 patients in each group. Joint arthrocentesis was performed to all patients followed by intra-articular BMAC injection in Group I. While Group II received HA acid injection ResultsA trend towards long term joint repair at 12 and 18 months follow up period was observed in the bone marrow aspirate concentrate (BMAC) group as a therapeutic modality for TMJ OA by providing necessary growth factors and anti-inflammatories that impedes the progression of the osteoarthritic degeneration. On the contrary to the viscosupplementary action of hyaluronic acid (HA) that showed relapse of patients conditions. ConclusionBone marrow aspirate concentrate (BMAC) is able to reverse the degenerative effects of TMJ OA however,further studies are mandatory with larger population and longer follow-up time.

BNTA attenuates temporomandibular joint osteoarthritis progression by directly targeting ALDH3A1: An in vivo and in vitro study

BNTA is known to have a therapeutic effect on knee osteoarthritis and inflammatory osteoclastogenesis. However, the protective effect of BNTA regarding temporomandibular mandibular joint osteoarthritis (TMJOA) and its underlying mechanism and physiological target remains unclear. In the present study, BNTA ameliorated cartilage degradation and inflammation responses in monosodium iodoacetate (MIA)-induced TMJOA in vivo. In IL-1β-induced condylar chondrocytes, BNTA prevents oxidative stress, inflammatory responses and increasing synthesis of cartilage extracellular matrix through activating nuclear factor-E2-related factor 2 (NRF2) signaling. Suppression of NRF2 signaling abolishes the protective effect of BNTA in TMJOA. Notably, BNTA may bind directly to ALDH3A1 and act as a stabilizer, as evidenced by drug affinity responsive target stability assay (DARTS), cellular thermal shift assay (CETSA) and molecular docking results. Further investigation of the underlying molecular and cellular mechanism infers a positive correlation of ALDH3A1 regulating NRF2 signaling. In conclusion, BNTA may attenuate TMJOA progression via the ALDH3A1/NRF2 axis, inferring that BNTA is a therapeutic target for treating temporomandibular mandibular joint osteoarthritis.

MiR-335-5p inhibits endochondral ossification by directly targeting SP1 in TMJ OA.

During the development of temporomandibular joint osteoarthritis, endochondral ossification is compromised which leads to condylar degeneration; miR-335-5p in endochondral ossification in osteoarthritic condylar cartilage tissue remains unclear. Up-regulated microRNA and its target gene were searched for endochondral ossification in osteoarthritis articular cartilage. The effect of increased or decreased miR-335-5p on endochondral ossification was evaluated by transfecting miR-335-5p mimics or miR-335-5p inhibitor in vitro in chondrocytes C28/I2. Finally, we injected the temporomandibular joint of rats intra-articularly with agomiR-335 in a unilateral anterior crossbite rat model to determine the in vivo regulation of miR-335. After the onset of temporomandibular joint osteoarthritis, miR-335-5p levels were gradually up-regulated, whereas endochondral ossification-related genes were down-regulated in condylar cartilage specimens. Our results showed that miR-335 inhibited endochondral ossification after administration of a miR-335 antagonist into the temporomandibular joint articular cavity of a unilateral anterior crossbite rat model. AgomiR-335, a miR-335 agonist, inhibited matrix mineralization in fibrocartilage stem cells in vitro and then miR-335-5p negatively regulated chondrocyte activity by directly targeting SP1 via promoting transforming growth factor-β/Smad signalling. miR-335-5p can significantly inhibit endochondral ossification; therefore, its inhibition may be beneficial for the treatment of temporomandibular joint osteoarthritis.

Comparing apparent diffusion coefficient values of the masticatory muscles on diffusion‐weighted magnetic resonance imaging in patients with temporomandibular joint osteoarthrosis

AbstractAimThis study aimed to compare the apparent diffusion coefficient (ADC) values of the masticatory muscles between patients with and without temporomandibular joint osteoarthritis (TMJ‐OA) on diffusion‐weighted magnetic resonance imaging.MethodsThis prospective study included 120 patients with temporomandibular disorders (TMD), including 60 patients with TMJ‐OA and 60 without TMJ‐OA, and 60 without TMD patients. All patients underwent magnetic resonance imaging of the TMJs at our hospital between November 2011 and January 2017. The regions of interest included the right and left lateral pterygoid muscles, medial pterygoid muscles, and masseter muscles on axial slices. Magnetic resonance images from the TMJ‐OA and control groups were independently evaluated by two oral and maxillofacial radiologists. ADC values were compared between the two groups using Mann–Whitney U tests.ResultsThe respective mean ADC values of the lateral pterygoid muscles in patients with TMJ‐OA and controls were 1.18 × 10−3 and 1.33 × 10−3 mm2/s, respectively. Those for the medial pterygoid muscles were 1.14 × 10−3 and 1.25 × 10−3 mm2/s, while those for the masseter muscles were 1.20 × 10−3 and 1.28 × 10−3 mm2/s, respectively. The mean ADC values of the normal lateral pterygoid, normal medial pterygoid, and normal masseter muscles were 1.29 × 10−3, 1.09 × 10−3, and 1.08 × 10−3 mm2/s, respectively.ConclusionAmong patients with TMDs, the ADC values of the masticatory muscles were significantly higher in patients without TMJ‐OA than in those with TMJ‐OA.

Comparison of Four Treatment Protocols with Intra-Articular Medium Molecular Weight Hyaluronic Acid in Induced Temporomandibular Osteoarthritis: An Experimental Study.

The aim was to compare the effect between a single intra-articular infiltration (1i) and two infiltrations (2i) of medium molecular weight hyaluronic acid (MMW-HA) of high viscosity (HV) and low viscosity (LV) on the histopathological characteristics of temporomandibular joint (TMJ) osteoarthritis (OA) induced in rabbits. An experimental study was conducted on Oryctolagus cuniculus rabbits, including 42 TMJs, distributed between (1) TMJ-C, control group; (2) TMJ-OA, group with OA; (3) TMJ-OA-wt, group with untreated OA; (4) group treated with HA-HV-1i; (5) group treated with HA-HV-2i; (6) group treated with HA-LV-1i; and (7) group treated with HA-LV-2i. The results were evaluated using the Osteoarthritis Research Society International (OARSI) scale and descriptive histology considering the mandibular condyle (MC), the articular disc (AD), and the mandibular fossa (MF). The Kruskal-Wallis test was used for the statistical analysis, considering p < 0.05 significant. All treated groups significantly decreased the severity of OA compared to the TMJ-OA-wt group. The HA-HV-2i group showed significant differences in the degree of OA from the TMJ-OA group. The degree of OA in the HA-HV-2i group was significantly lower than in the HA-LV-1i, HA-LV-2i, and HA-HV-1i groups. The protocol that showed better results in repairing the joint was HA-HV-2i. There are histological differences depending on the protocol of the preparation used: two infiltrations seem to be better than one, and when applying two doses, high viscosity shows better results.

Loss of miR-204 and miR-211 shifts osteochondral balance and causes temporomandibular joint osteoarthritis.

Temporomandibular joint (TMJ) osteoarthritis (OA) is a common type of TMJ disorders causing pain and dysfunction in the jaw and surrounding tissues. The causes for TMJ OA are unknown and the underlying mechanism remains to be identified. In this study, we generated genetically-modified mice deficient of two homologous microRNAs, miR-204 and miR-211, both of which were confirmed by in situ hybridization to be expressed in multiple TMJ tissues, including condylar cartilage, articular eminence, and TMJ disc. Importantly, the loss-of-function of miR-204 and miR-211 caused an age-dependent progressive OA-like phenotype, including cartilage degradation and abnormal subchondral bone remodeling. Mechanistically, the TMJ joint deficient of the two microRNAs demonstrated a significant accumulation of RUNX2, a protein directly targeted by miR-204/-211, and upregulations of β-catenin, suggesting a disrupted balance between osteogenesis and chondrogenesis in the TMJ, which may underlie TMJ OA. Moreover, the TMJ with miR-204/-211 loss-of-function displayed an aberrant alteration in both collagen component and cartilage-degrading enzymes and exhibited exacerbated orofacial allodynia, corroborating the degenerative and painful nature of TMJ OA. Together, our results establish a key role of miR-204/-211 in maintaining the osteochondral homeostasis of the TMJ and counteracting OA pathogenesis through repressing the pro-osteogenic factors including RUNX2 and β-catenin.