Temporomandibular Joint Osteoarthritis Research Articles

Primed IFN-γ-umbilical cord stem cells ameliorate temporomandibular joint osteoarthritis.

Temporomandibular joint osteoarthritis (TMJOA) is a degenerative disorder affecting the temporomandibular joint (TMJ), marked by persistent inflammation and structural damage to the joint. Only symptomatic treatment is available for managing TMJOA. Human umbilical cord mesenchymal stem cells (hUC-MSCs) show potential for treating TMJOA via their immune modulating actions in the disease area. Additionally, stimulation of inflammatory cytokine such as interferon-gamma in hUC-MSCs improves the therapeutic activity of naïve stem cells. Emerging evidence indicates that macrophages play significant roles in regulating joint inflammation through diverse secreted mediators in the pathogenesis of TMJOA. This study was conducted to evaluate the effects of inflammatory cytokine-stimulated hUC-MSCs in repairing TMJOA-induced cartilage lesions and the role of macrophages in the disease. Our in vitro data showed that stimulated hUC-MSCs induce M2 polarization of macrophages and enhance the expression of anti-inflammatory molecules. These effects were subsequently validated in vivo. In a rat model of TMJOA, stimulated hUC-MSCs ameliorated inflammation and increased M2 macrophages ratio. Our results indicate that hUC-MSCs stimulated by inflammatory cytokines modulate the activation of M2 macrophages, thereby shifting the local osteoarthritis (OA) microenvironment towards a pro-chondrogenic state and facilitating cartilage repair in inflammatory conditions. Stimulating hUC-MSCs with inflammatory cytokines could potentially offer an effective therapeutic approach for TMJOA, with macrophages playing a pivotal role in immune modulation.

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

BackgroundExtracellular 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 methodsTo 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.ResultsMicro-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.ConclusionsDspp+/– 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.

A randomized controlled clinical trial of concentrated growth factor combined with sodium hyaluronate in the treatment of temporomandibular joint osteoarthritis

ObjectiveTo investigate the effect of concentrated growth factor (CGF) combined with sodium hyaluronate (SH) on temporomandibular joint osteoarthritis (TMJOA).MethodsSixty patients with TMJOA who were diagnosed by cone-beam computed tomography (CBCT) between March 2020 and March 2023 at the Stomatological Hospital of Xi’an Jiaotong University were randomly divided into a control group (n = 30) and an experimental group (n = 30). The patients in the experimental group were treated with CGF + SH, and those in the control group were treated with SH only. The visual analogue scale (VAS) score indicating pain in the temporomandibular joint (TMJ) area; the Helkimo Clinical Dysfunction Index (Di); and changes in condylar CBCT at the first visit and 2 weeks, 3 months and 6 months after treatment were recorded. The CBCT data of the patients in the experimental and control groups were collected, and the three-dimensional CBCT image sequences were imported into Mimics Medical 19.0 software in DICOM format for condylar reconstruction.ResultsThe VAS scores at 2 weeks, 3 months and 6 months after treatment were significantly lower in the experimental group than in the control group (P < 0.05), and the pain in the experimental group was significantly relieved. The Di was significantly lower in the experimental group than in the control group (P < 0.05), and the clinical function of the TMJ improved. After treatment, the CBCT score was significantly lower in the experimental group than in the control group (P < 0.05), and the condylar bone cortex was obviously repaired. Observation of the condylar bone cortex by three-dimensional reconstruction showed the same results as those obtained by CBCT.ConclusionCGF combined with SH is effective in the treatment of TMJOA and can improve muscle pain, TMJ pain, Impaired TMJ function, Impaired range of movement, Pain on movement of the mandible and promote bone repair.The registration number (TRN)ChiCTR2400082712.The date of registrationApril 5, 2024.

Synovial osteoclastogenesis mediated by chondrocyte-secreted TNFα promotes TMJ condylar resorption.

Insufficient occlusal support (IOS) frequently causes subchondral bone absorption in temporomandibular joint osteoarthritis, and the underlying mechanism requires further investigation. An IOS model was established by abrading rat molars. Micro-computed tomography was used to evaluate subchondral bone changes. Osteoclastogenesis of synovium-derived macrophages (SDMs) was confirmed by TRAP staining. Cartilage-specific TNFα depletion was achieved by intra-articular injection of adeno-associated virus carrying shRNA against murine TNFα under control of collagen type II. Invitro, chondrocytes were mechanically compressed and conditioned medium (CM) was collected to detect its ability to induce osteoclastogenesis of SDMs. Synovial osteoclastogenesis and condyle resorption were observed following IOS. TNFα level was elevated in hypertrophic chondrocytes after IOS. Synovial Wnt5a level increased, but Wnt3a level decreased after IOS. Depletion of TNFα in chondrocytes alleviated the synovial osteoclastogenesis and condyle bone resorption. Invitro compression of chondrocytes potentiated TNFα expression and secretion. The CM promoted osteoclastogenesis of SDMs, which were partially prohibited by TNFα neutralizing antibody. Furthermore, inhibition of Wnt3a facilitated osteoclastogenesis, whereas inhibition of Wnt5a partially suppressed osteoclastogenesis, of SDMs cultured in CM. Chondrocyte-secreted TNFα induced by IOS is a critical regulator of synovial osteoclastogenesis and subsequent condylar resorption, partially through non-canonical Wnt5a pathway.

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 challenge of ecological validity in temporomandibular disorders research.

To review the ecological validity of outcomes from current research involving temporomandibular disorders (TMDs), with an emphasis on chronic myofascial pain and the precocious development of degenerative disease of the temporomandibular joint (TMJ). Current approaches used to study TMDs in terms of neuromechanics, masticatory muscle behaviours, and the dynamics of the autonomic nervous system (ANS) were assessed for ecological validity in this review. In particular, the available literature was scrutinized regarding the effects of sampling, environmental and psychophysiological constraints and averaging data across biological rhythms. Validated computer-assisted numerical modelling of the neuromechanics used biological objective functions to accurately predict muscle activation patterns for jaw-loading tasks that were individual-specific. With respect to masticatory muscle behaviour, current findings refute the premise that sustained bruxing and clenching at high jaw-loading magnitudes were associated with painful TMDs such as myofascial pain. Concerning the role of the ANS in TMDs, there remains the need for personalized assessments based on biorhythms, and where the detection of dysregulated physiologic oscillators may inform interventions to relieve pain and restore normal function. Future human research which focuses on TMD myofascial pain or the precocious development and progression of TMJ degenerative joint disease requires experimental designs with ecological validity that capture objectively measured data which meaningfully reflect circadian and ultradian states.

Degenerative Temporomandibular Disorders: An Assessment of Bone Trabecular Structure Using Fractal Analysis in Digital Panoramic Radiographs.

Introduction Fractal analysis has proved to be a salient tool to quantitatively assess the qualitative changes in the bone trabeculae of patients with hyperparathyroidism, osteoporosis, and various temporomandibular disorders, including osteoarthritis (OA) and rheumatoid arthritis of temporomandibular joint (TMJ), in several previous studies. The purpose of this study was to use fractal analysis to assess alterations in the trabecular pattern of the mandibular condyle in patients with degenerative temporomandibular disorders. Materials and methods This study comprised 98 subjects with 49 subjects in the study group and 49 subjects in the control group, aged 18-50 years. Age and sex in the control group were matched to those in the case group. The subjects were assessed clinically with the Diagnostic Criteria for Temporomandibular Disorders. Digital panoramic X-ray equipment with set parameters of 70 kvp, 8 mA, and 16-second exposure duration was used to take panoramic radiographs. Fractal analysis was done and the calculated fractal dimension value was obtained usingImageJ version 1.48 software (National Institutes of Health, Bethesda, MD). The same observer used Muir and Goss's method to rate the total degenerative changes in the condylar surfaces, which were substantiated by the calculated fractal dimension value. The data were statistically analyzed. Results The results revealed a significant difference (p-value = 0.041) between the mean fractal valuein the case group's (1.35) and the control group's (1.38) left sides whereas the differences in the mean fractal values between the case and control groups on the right side was not significant (p-value = 0.49). Conclusion It is recommended to use the fractal dimension value and the total degenerative severity score together to quantify degenerative changes in the TMJ OA rather than exclusively relying on fractal value.

Correlations with clinical and radiologic findings and prevalence of osteopenia/osteoporosis in the patients with bilateral temporomandibular joint osteoarthritis

This study aimed to evaluate the prevalence of osteopenia/osteoporosis in patients with bilateral temporomandibular joint osteoarthritis (TMJ-OA) and its correlations with clinical and radiological findings. A total of 95 patients with bilateral TMJ-OA diagnosed by CBCT were included in the study. Clinical and radiological findings and bone mineral density (BMD) scores were recorded. Descriptive statistics and the Spearman rho correlation tests were performed. Osteopenia/osteoporosis was found in 44 of 95 patients (46.32 %) (30, osteopenia; 14 osteoporosis). Osteopenia/osteoporosis is significantly associated with postmenopausal status and age over 40 years, but it is not associated with clinical and radiological findings of TMJ-OA. Patients with bilateral TMJ-OA have a high prevalence of osteopenia/osteoporosis.

Pengembangan Terapi Regeneratif pada Osteoartritis Sendi Temporomandibula : Telaah Pustaka

Temporomandibular joint osteoarthritis (TMJ OA) is a degenerative condition that affects the temporomandibular joint, causing pain, stiffness, and limited jaw movement. Conventional therapies such as medications, physical therapy, and surgery often only provide temporary solutions and cannot permanently restore joint function. Therefore, regenerative therapy has emerged as a promising approach to address TMJ OA by harnessing the body's natural healing potential. This literature review aims to provide a comprehensive overview of the development of regenerative therapies for TMJ OA, including therapeutic strategies, challenges, and future opportunities. Regenerative therapies for TMJ OA encompass various strategies, such as stem cell injections, biomaterial scaffolds, growth factors, gene therapy, and combination therapies. Although regenerative therapies have shown promising results in preclinical studies, several challenges remain, such as safety, efficacy, and translation into clinical applications. It can be concluded that regenerative therapy offers an innovative and potential approach to addressing TMJ OA by utilizing the body's natural healing capabilities, with the hope of restoring joint function and improving the quality of life for TMJ OA patients in the future.

Comparison of the effectiveness of treatment of temporomandibular joint osteoarthritis between monotherapy with splints and splints in combination with platelet-rich plasma

Today there is a tendency to increase the prevalence of Temporomandibular Joint Osteoarthritis (TMJ) osteoarthritis, which is a chronic degenerative joint disease. According to international statistics, 28–38% of people in the age group of 9–90 years have signs of TMJ osteoarthritis. The aim of our study was to compare the effectiveness of treatment of TMJ osteoarthritis between monotherapy with splints and splinys in combination with Platelet-Rich Plasma (PRP). The experiment involved 8 patients, divided into 2 level groups. The control group (4 patients) received treatment with splints, the experimental group – splits with PRP therapy. The effectiveness of treatment was assessed by measuring the radiological density of the cortical plate of the mandibular head according to the Hounsfield scale, the degree of mouth opening, filling out a Visual Analogue Scale (VAS) and a questionnaire at the end of treatment. According to the results of the study, the experimental group received more effective treatment, which is confirmed by the VAS, the degree of mouth opening and changes in the radiological density of the cortical plate of the articular head. At the end of the treatment, patients completed a questionnaire about the improvement of their condition, where 0 points meant no effect from the treatment, and 10 points meant a subjective feeling of complete recovery. The arithmetic mean of the improvement scores in the control group was 6.75, and in the experimental group – 9.00 points. Based on the results of the experiment, we can state that the effectiveness of treatment of TMJ osteoarthritis with splints in combination with PRP therapy is greater than that of monotherapy with occlusal splints. Therefore, if the patient has no contraindications to treatment with platelet-rich plasma, we can recommend the use of splits in combination with PRP therapy for the treatment of temporomandibular joint osteoarthritis. Keywords: degenerative diseases, radiological density, articular head.

A loss of primary cilia by a reduction in mTOR signaling correlates with age-related deteriorations in condylar cartilage.

Age-related deterioration of condylar cartilage is an etiological factor in temporomandibular joint-osteoarthritis (TMJ-OA). However, its underlying mechanism remains unknown. Therefore, we examined age-related changes and the relationship between mTOR signaling and primary cilia in condylar cartilage to determine the intrinsic mechanisms of age-related TMJ-OA. Age-related morphological changes were analyzed using micro-computed tomography and safranin O-stained histological samples of the mandibular condyle of C57BL/6J mice (up to 78weeks old). Immunohistochemistry was used to assess the activity of mTOR signaling, primary cilia frequency, and Golgi size of condylar chondrocytes. Four-week-old mice receiving an 11-week series of intraperitoneal injections of rapamycin, a potent mTOR signaling inhibitor, were used for the histological evaluation of the condylar cartilage. The condylar cartilage demonstrated an age-related reduction in cartilage area, including chondrocyte size, cell density, and cell size distribution. The Golgi size, primary cilia frequency, and mTOR signaling also decreased with age. Rapamycin injections resulted in both diminished cartilage area and cell size, resembling the phenotypes observed in aged mice. Rapamycin-injected mice also exhibited a smaller Golgi size and lower primary cilia frequency in condylar cartilage. We demonstrated that a loss of primary cilia due to a decline in mTOR signaling was correlated with age-related deteriorations in condylar cartilage. Our findings provide new insights into the tissue homeostasis of condylar cartilage, contributing to understanding the etiology of age-related TMJ-OA.

TRIM52 knockdown inhibits proliferation, inflammatory responses and oxidative stress in IL-1β-induced synovial fibroblasts to alleviate temporomandibular joint osteoarthritis.

To explore the mechanism of tripartite motif 52 (TRIM52) in the progression of temporomandibular joint osteoarthritis (TMJOA). Gene and protein expression were tested by quantitative real-time polymerase chain reaction and western blot, respectively. The levels of pro-inflammatory cytokines and oxidative stress factors were evaluated using enzyme-linked immunosorbent assay and biochemical kit, respectively. Cell counting kit-8 and 5-ethynyl-2'-deoxyuridine assays were carried out to assess cell proliferation. Immunofluorescence was used to detect the expression of CD68 and Vimentin in primary synovial fibroblasts (SFs). Haematoxylin and eosin staining and Safranin O/Fast green were used to evaluate the pathological damage of synovial and cartilage tissue in rats. TRIM52 was upregulated in the synovial tissue and SFs in patients with TMJOA. Interleukin (IL)-1β treatment upregulated TRIM52 expression in TMJOA SFs and normal SF (NSF), promoting cell proliferation, inflammatory response and oxidative stress in NSF, SFs. Silence of TRIM52 relieved the cell proliferation, inflammatory response and oxidative stress induced by IL-1β in SFs, while overexpression of TRIM52 enhanced IL-1β induction. Meanwhile, IL-1β induction activated toll-like receptor 4 (TLR4)/nuclear factor (NF)-κB pathway, which was augmented by upregulation of TRIM52 in NSF, and was attenuated by TRIM52 knockdown in SFs. Besides, pyrrolidinedithiocarbamic acid ameliorated IL-1β-induced proliferation and inflammatory response by inhibiting TLR4/NF-κB signalling. Meanwhile, TRIM52 knockdown inhibited cell proliferation, oxidative stress and inflammatory response in IL-1β-induced SFs through downregulation of TLR4. TRIM52 promoted cell proliferation, inflammatory response, and oxidative stress in IL-1β-induced SFs. The above functions were mediated by the activation of TLR4/NF- κB signal pathway.

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.

Use of platelet-rich plasma isolated or in combination in osteoarthritis of the temporomandibular joint: a systematic review

Introduction: Temporomandibular joint osteoarthritis (TMJ-OA) is a common disease in the oral and maxillofacial regions and is the most serious type. Among temporomandibular disorders, TMJ-OA accounts for 18% to 85% of all cases. The use of platelet-rich plasma (PRP) has been highlighted, as well as in combination with other types of treatments such as hyaluronic acid, arthrocentesis, and corticosteroids. Objective: to highlight the main clinical outcomes of the treatment of osteoarthritis of the temporomandibular joint through the injectable use of platelet-rich plasma, alone or in combination with other types of treatment. Methods: The research and development of the work were carried out from December 2023 to February 2024 in the databases Scopus, PubMed, Science Direct, and Scielo, using scientific articles from 2013 to 2023, following the PRISMA rules. The quality of the studies was based on the GRADE instrument and the risk of bias was based on the Cochrane instrument (Funnel Plot). Results and Conclusion: A total of 178 studies were found that were subjected to eligibility analysis. The final sample had 45 eligible studies and 31 studies were described in the systematic review. Most studies showed homogeneity in their results, with X2 =66.7% &gt;50%, with p&lt;0.05. The symmetric funnel plot did not suggest a risk of bias among studies with a small sample size. The results showed that platelet-rich plasma performed better than hyaluronic acid in the treatment of osteoarthritis of the temporomandibular joint during longterm follow-up in terms of reducing pain and increasing interincisal distance. Combined injection of hyaluronic acid and platelet-rich plasma after arthrocentesis is more effective than hyaluronic acid or platelet-rich plasma alone in the treatment of osteoarthritis of the temporomandibular joint, as well as platelet-rich plasma with hyaluronic acid after arthrocentesis showed significant clinical efficacy long-term concerning pain relief. Furthermore, it was found that intra-articular injections of platelet-rich plasma reduced pain on palpation of the temporomandibular joint more effectively compared to hyaluronic acid and corticosteroids. Platelet-rich plasma injection can significantly improve pain, mouth opening, abnormal joint sound, and jaw function in patients with temporomandibular joint osteoarthritis, and has a good repair effect on condylar bone defects. Furthermore, platelet-rich plasma injection combined with physical therapy can effectively control medium and long-term pain in patients.

Metabolic profiling of synovial fluid in human temporomandibular joint osteoarthritis.

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. 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. 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. 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.

Comparative analysis of temporomandibular joint morphology in degenerative joint disease: A cone-beam CT study in patients with and without arthralgia

ObjectivesThis cross-sectional study aimed to compare, by using Cone-Beam Computed Tomography (CBCT), temporomandibular joint (TMJ) morphology among patients with degenerative joint disease (DJD) with or without arthralgia, as well as a control group. Methods: Thirty-one patients and their respective CBCT TMJ exams were assessed. These individuals were selected from an Orofacial Pain Service and classified into three groups based on the Diagnostic Criteria for Temporomandibular Disorders (DC/TMD): group 1 (10 patients with TMJ DJD and arthralgia), group 2 (11 patients with TMJ DJD without pain), and group 3 (the control group, consisting of 10 healthy individuals without any signs or symptoms of TMD). A second examiner, who was calibrated and blinded for the patient's diagnosis, evaluated the CBCT images. Results: Group 1 showed a statistically significant association with the variables of erosion (p = 0.003) and osteophyte (p = 0.04) on the condyle surface, as well as concentric condyle position with reduced joint space (p = 0.01). The Kappa concordance index between the clinical diagnosis of DC/TMD and CBCT images was k = 0.134 (p ≤ 0.001). Conclusion: The presence of erosion, osteophyte, and concentric condyle position with reduced joint space was statistically associated with DJD and ongoing TMJ joint pain.

Equine Models of Temporomandibular Joint Osteoarthritis: A Review of Feasibility, Biomarkers, and Molecular Signaling.

Osteoarthritis (OA) of the temporomandibular joint (TMJ) occurs spontaneously in humans and various animal species, including horses. In humans, obtaining tissue samples is challenging and clinical symptoms appear late in the disease progression. Therefore, genetically modified, induced, and naturally occurring animal models play a crucial role in understanding the pathogenesis and evaluating potential therapeutic interventions for TMJ OA. Among the naturally occurring models, the equine TMJ OA model is characterized by slow, age-related progression, a wide range of clinical examinations, and imaging modalities that can be performed on horses, as well as easy tissue and synovial fluid collection. The morphological and functional similarities of TMJ structures in both species make the equine model of TMJ OA an excellent opportunity to track disease progression and response to treatment. However, much work remains to be carried out to determine the utility of human TMJ OA biomarkers in horses. Among the main TMJ OA biomarkers, IL-1, IL-6, TGF-β, TNF-α, and PGE2 have been recently investigated in the equine model. However, the majority of biomarkers for cartilage degradation, chondrocyte hypertrophy, angiogenesis, and TMJ overload-as well as any of the main signaling pathways-have not been studied so far. Therefore, it would be advisable to focus further research on equine specimens, considering both mediators and signaling.

Sex dependent differences of temporomandibular condylar bone mineral density distribution

ABSTRACT Objective The objective of this study was to examine whether bone mineral density (BMD) distribution in the mandibular condyle and facial morphology are associated with temporomandibular joint osteoarthritis (TMJ OA) using clinical cone beam computed tomography (CBCT) images. Methods CBCT images of 35 adults (16 male and 19 female) were examined to obtain TMJ OA counts, cephalometric analyses, and histograms of gray values that are proportional to BMD. Mean, standard deviation (SD), and low and high gray values at the 5th and 95th percentiles (Low5 and High5) of the histograms were measured. Results The female group had significantly higher values of TMJ OA counts, mean, and SD on the right mandibular condyle, High5 on both sides, and all gray value parameters for total (right + left) than the male group. Conclusion Comprehensive analysis of BMD distribution in the mandibular condyle can provide useful information for prognosis of TMJ OA.

Effects of endoplasmic reticulum stress on chondrocyte apoptosis via the PI3K/AKT signaling pathway

Chondrocytes undergo endoplasmic reticulum stress (ERS)-induced apoptosis under abnormal stimulation. However, the underlying molecular mechanism remains unclear. We investigated the regulatory effect of the PI3K/AKT signaling pathway on ERS and its effect on chondrocyte apoptosis. In addition, we established a unilateral anterior crossbite (UAC) model in rats to induce temporomandibular joint osteoarthritis (TMJOA). Chondrocytes were isolated from the temporomandibular joints and treated with lipopolysaccharide (LPS) in vitro. Protein expression of ERS and apoptosis markers (GRP78 and CASP12) was analyzed by immunohistochemistry and western blotting. The expression of GRP78, CASP12, p-PI3K, and p-AKT significantly increased in the UAC group. LY294002, a PI3K/AKT signaling pathway inhibitor, reduced the protein expression of GRP78, ATF4, CHOP, and CASP12, whereas 740 Y-P, an activation agent, elevated the expression of proteins GRP78, ATF4, CHOP, and CASP12. In the present study, UAC and LPS stimulation induced apoptosis of chondrocytes in the ERS pathway. Inhibition of the PI3K/AKT signaling pathway reduced ERS-induced chondrocyte apoptosis.

Conditioned Medium From Stem Cells of Human Exfoliated Deciduous Teeth Alleviates Mouse Osteoarthritis by Inducing sFRP1-Expressing M2 Macrophages.

Intravenous administration of conditioned medium from stem cells of human exfoliated deciduous teeth (SHED-CM) regenerates mechanically injured osteochondral tissues in mouse temporomandibular joint osteoarthritis (TMJOA). However, the underlying therapeutic mechanisms remain unclear. Here, we showed that SHED-CM alleviated injured TMJ by inducing anti-inflammatory M2 macrophages in the synovium. Depletion of M2 by Mannosylated Clodrosome abolished the osteochondral repair activities of SHED-CM. Administration of CM from M2-induced by SHED-CM (M2-CM) effectively ameliorated mouse TMJOA by inhibiting chondrocyte inflammation and matrix degradation while enhancing chondrocyte proliferation and matrix formation. Notably, in vitro, M2-CM directly suppressed the catabolic activities while enhancing the anabolic activities of interleukin-1β-stimulated mouse primary chondrocytes. M2-CM also inhibited receptor activator of nuclear factor NF-κB ligand-induced osteoclastogenesis in RAW264.7 cells. Secretome analysis of M2-CM and M0-CM revealed that 5 proteins related to anti-inflammation and/or osteochondrogenesis were enriched in M2-CM. Of these proteins, the Wnt signal antagonist, secreted frizzled-related protein 1 (sFRP1), was the most abundant and played an essential role in the shift to anabolic chondrocytes, suggesting that M2 ameliorated TMJOA partly through sFRP1. This study suggests that secretome from SHED exerted remarkable osteochondral regeneration activities in TMJOA through the induction of sFRP1-expressing tissue-repair M2 macrophages.