RESUMEN
Background: The role of autoimmune diseases (ADs) in temporomandibular disorders (TMDs) has been emphasized in observational studies. However, whether the causation exists is unclear, and controversy remains about which specific disorder is destructive in TMDs. This Mendelian randomization (MR) study aims to estimate the causal effect of common ADs on TMDs. Methods: Genetic data from published genome-wide association studies for fourteen common ADs, specifically multiple sclerosis (MS, N = 15,283), ankylosing spondylitis (AS, N = 22,647), asthma (N = 408,422), celiac disease (N = 15,283), Graves' disease (N = 458,620), Hashimoto thyroiditis (N = 395,640), primary biliary cirrhosis (PBC, N = 11,375), primary sclerosing cholangitis (PSC, N = 14,890), psoriasis vulgaris (N = 483,174), rheumatoid arthritis (RA, N = 417,256), systemic lupus erythematosus (SLE, N = 23,210), Type 1 diabetes (T1D, N = 520,580), inflammatory bowel disease (IBD, N = 34,652), and Sjogren's syndrome (SS, N = 407,746) were collected. Additionally, the latest summary-level data for TMDs (N = 228,812) were extracted from the FinnGen database. The overall effects of each immune traits were assessed via inverse-variance weighted (IVW), weighted median, and MR-Egger methods, and performed extensive sensitivity analyses. Finally, 731 immune cell phenotypes (N = 3,757) were analyzed for their mediating role in the significant causality. Results: Univariable MR analyses revealed that genetically predicted RA (IVW OR: 1.12, 95% CI: 1.05-1.19, p < 0.001) and MS (IVW OR: 1.06, 95% CI: 1.03-1.10, p = 0.001) were associated with increased risk of TMDs. Two out of 731 immune cell phenotypes were identified as causal mediators in the associations of RA with TMDs, including "CD25++ CD8+ T cell % CD8+ T cell" (mediation proportion: 6.2%) and "CD3 on activated CD4 regulatory T cell" (5.4%). Additionally, "CD127 on granulocyte" mediated 10.6% of the total effect of MS on TMDs. No reverse directions, heterogeneity, and pleiotropy were detected in the analyses (p > 0.05). Conclusion: This MR study provides new evidence regarding the causal impact of genetic predisposition to RA or MS on the increased risk of TMDs, potentially mediated by the modulation of immune cells. These findings highlight the importance for clinicians to pay more attention to patients with RA or MS when consulting for temporomandibular discomfort. The mediating role of specific immune cells is proposed but needs further investigation.
Asunto(s)
Enfermedades Autoinmunes , Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Trastornos de la Articulación Temporomandibular , Humanos , Enfermedades Autoinmunes/genética , Enfermedades Autoinmunes/inmunología , Enfermedades Autoinmunes/etiología , Trastornos de la Articulación Temporomandibular/genética , Trastornos de la Articulación Temporomandibular/etiología , Trastornos de la Articulación Temporomandibular/inmunología , Predisposición Genética a la Enfermedad , Polimorfismo de Nucleótido SimpleRESUMEN
Temporomandibular disorder (TMD) is an oral dentofacial disease that is related to multiple factors such as disordered dental occlusion, emotional stress, and immune responses. In the past decades, tumor necrosis factor-alpha (TNF-α), a pleiotropic cytokine, has provided valuable insight into the pathogenesis of TMD, particularly in settings associated with inflammation. It is thought that TNF-α participates in the pathogenesis of TMD by triggering immune responses, deteriorating bone and cartilage, and mediating pain in the temporomandibular joint (TMJ). Initially, TNF-α plays the role of "master regulator" in the complex immune network by increasing or decreasing the production of other inflammatory cytokines. Then, the effects of TNF-α on cells, particularly on chondrocytes and synovial fibroblasts, result in pathologic cartilage degradation in TMD. Additionally, multiple downstream cytokines induced by TNF-α and neuropeptides can regulate central sensitization and inflammatory pain in TMD. Previous studies have also found some therapies target TMD by reducing the production of TNF-α or blocking TNF-α-induced pathways. All this evidence highlights the numerous associations between TNF-α and TMD; however, they are currently not fully understood and further investigations are still required for specific mechanisms and treatments targeting specific pathways. Therefore, in this review, we explored general mechanisms of TNF-α, with a focus on molecules in TNF-α-mediated pathways and their potential roles in TMD treatment. In view of the high clinical prevalence rate of TMD and damage to patients' QOL, this review provides adequate evidence for studying links between inflammation and TMD in further research and investigation.
Asunto(s)
Inflamación/metabolismo , Trastornos de la Articulación Temporomandibular/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Huesos/metabolismo , Huesos/patología , Cartílago/metabolismo , Cartílago/patología , Condrocitos/metabolismo , Citocinas/metabolismo , Fibroblastos/metabolismo , Humanos , Inflamación/complicaciones , Dolor Musculoesquelético/metabolismo , Articulación Temporomandibular/metabolismo , Articulación Temporomandibular/patología , Trastornos de la Articulación Temporomandibular/etiología , Trastornos de la Articulación Temporomandibular/inmunología , Trastornos de la Articulación Temporomandibular/patología , Factor de Necrosis Tumoral alfa/inmunologíaRESUMEN
Aim: Inflammatory idiopathic myopathies (IIMs) are inflammatory processes affecting skeletal musculature and extramuscular organs. Temporomandibular disorders (TMD) involve jaw muscles and temporomandibular joint. The aim of this observational study was to investigate the prevalence of the main TMD symptoms and signs as well as oral implications in IIM patients. Methods: The study group included 54 patients (42 women and 12 men), 22 of whom affected by dermatomyositis (DM), 29 by polymyositis (PM) and 3 by inclusion body myositis (IBM). A group of 54 patients not affected by this disease, served as CG. Oral and TMD signs and symptoms were evaluated by means of a questionnaire and through clinical examination. Results: About oral symptoms, the study group complained more frequently dysgeusia, with loss of taste or unpleasant taste (p<0.0001) and feeling of burning mouth (9.4% versus 0 controls). Xerostomia was more prevalent in the study group respect to the CG (p<0.0001). Dysphagia was reported by 48.1% of IIM patients while was absent in CG (p<0.0001). About oral signs, cheilitis (p<0.05) and oral ulcers (p<0.05) were significantly more frequent in CG. As regard to TMD symptoms, arthralgia and tinnitus didn't showed significant differences between the two groups, while neck/shoulders and masticatory muscle pain was significantly more referred in IIM patients than in the CG (p<0.05). About TMJ signs, sounds were overlapping in the two groups: click=11.1% in both IIM patients and CG (p>0.05), crepitation in 11.1% of IIM and 9.3% of controls (p>0.05). No significant difference was detected about deflection (9.3%, p>0.05), while deviation was wider in CG (p<0.05). Active opening and lateralities showed no significant differences, while endfeel was significantly increased in IIM group for a higher presence of muscular contracture. Bruxism was present only in CG. Conclusion: The data collected from this observational study seem to support the existence of a relationship between the prevalence of TMD symptoms and signs as well as oral features in patients with myositis. A remarkable reduction of salivary flow and dysphagia were more frequent and severe in IIM patients, as well as muscle contracture and myofacial pain evoked by palpation, this result being highly significant.
Asunto(s)
Dermatomiositis/complicaciones , Disgeusia/epidemiología , Miositis por Cuerpos de Inclusión/complicaciones , Trastornos de la Articulación Temporomandibular/epidemiología , Xerostomía/epidemiología , Anciano , Estudios de Casos y Controles , Dermatomiositis/inmunología , Disgeusia/diagnóstico , Disgeusia/inmunología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Miositis por Cuerpos de Inclusión/inmunología , Prevalencia , Trastornos de la Articulación Temporomandibular/diagnóstico , Trastornos de la Articulación Temporomandibular/inmunología , Xerostomía/diagnóstico , Xerostomía/inmunologíaRESUMEN
The underlying mechanisms and treatment of painful temporomandibular disorders (TMDs) are important but understudied topics in craniofacial research. As a group of musculoskeletal diseases, the onset of painful TMD is proved to be a result of disturbance of multiple systems. Recently, emerging evidence has revealed the involvement of neuroimmune interactions in painful TMD. Inflammatory factors play an important role in peripheral sensitization of temporomandibular joint (TMJ), and neurogenic inflammation in turn enhances TMJs dysfunction in TMD. Furthermore, centralized neuroimmune communications contribute to neuron excitability amplification, leading to pain sensitization, and is also responsible for chronic TMD pain and other CNS symptoms. Therapeutics targeting neuroimmune interactions may shed light on new approaches for treating TMD. In this review, we will discuss the role of neuroimmune interactions in the onset of painful TMD from the peripheral and centralized perspectives, and how understanding this mechanism could provide new treatment options. Insights into the neuroimmune interactions within TMJs and painful TMD would broaden the knowledge of mechanisms and treatments of this multifactorial disease.
Asunto(s)
Neuroinmunomodulación , Dolor/complicaciones , Dolor/inmunología , Trastornos de la Articulación Temporomandibular/inmunología , Trastornos de la Articulación Temporomandibular/terapia , Progresión de la Enfermedad , Humanos , Modelos Biológicos , Trastornos de la Articulación Temporomandibular/patología , Trastornos de la Articulación Temporomandibular/fisiopatologíaRESUMEN
OBJECTIVE(S): It is well appreciated that traditional analgesic delivery routes used to treat pain associated with temporomandibular disorder (TMD) often have harmful unintended side effects as a consequence of systemic distribution. Further, localized delivery of analgesic medication via intra-articular injections involves a different set of issues limiting their clinical viability. As an option, transdermal analgesic delivery provides for prolonged pain relief and flexibility in dose administration, while limiting systemic exposure and minimizing adverse events. Incorporation of a novel electroporation technique may further increase transdermal drug penetration into synovial tissue/fluid and enhance pain reduction. The present feasibility study compares the effectiveness of an electroporation-enhanced transdermal application of diclofenac sodium to a conventional intra-articular injection of triamcinolone acetonide suspension (corticosteroids) to treat patients with TMD associated pain. METHODS: Pre- and post-treatment maximal incisal mouth opening (MIO), pain visual analog scale (VAS) and surface electromyography (EMG) of 22 patients treated with electroporation-enhanced diclofenac and 37 patients treated with corticosteroids injections were collected and analyzed. RESULTS: In general, patients treated with electroporation exhibited better results in terms of pain improvement (corrected p-value = .01) compared to the standard treatment, but both methods were similarly effective for improvement of MIO (corrected p-value = .71) and improvement of all EMG indices (corrected p-values ≥ .05). CONCLUSION: The enhancing effect of electroporation in transdermal delivery of diclofenac sodium was demonstrated by decreased pain, increase MIO and EMG improvement to normal values. Its analgesic and inflammatory results are comparable with standard treatment offered by corticosteroids.
Asunto(s)
Antiinflamatorios no Esteroideos/administración & dosificación , Artralgia/tratamiento farmacológico , Diclofenaco/administración & dosificación , Electroquimioterapia/métodos , Trastornos de la Articulación Temporomandibular/tratamiento farmacológico , Adulto , Anciano , Artralgia/diagnóstico , Artralgia/inmunología , Electroquimioterapia/estadística & datos numéricos , Estudios de Factibilidad , Femenino , Glucocorticoides/administración & dosificación , Humanos , Inyecciones Intraarticulares/efectos adversos , Inyecciones Intraarticulares/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Dimensión del Dolor/estadística & datos numéricos , Proyectos Piloto , Estudios Prospectivos , Trastornos de la Articulación Temporomandibular/complicaciones , Trastornos de la Articulación Temporomandibular/inmunología , Resultado del Tratamiento , Triamcinolona Acetonida/administración & dosificaciónRESUMEN
The temporomandibular joint (TMJ) is a fibrocartilaginous tissue critical for chewing and speaking. In patients with temporomandibular disorders (TMDs), permanent tissue loss can occur. Recapitulating the complexity of TMDs in animal models is difficult, yet critical for the advent of new therapies. Synovial fluid from diseased human samples revealed elevated levels of tumor necrosis factor alpha (TNF-alpha). Here, we propose to recapitulate these findings in mice by subjecting murine TMJs with TNF-alpha or CFA (Complete Freund's Adjuvant) in mandibular condyle explant cultures and by local delivery in vivo using TMJ intra-articular injections. Both TNF-alpha and CFA delivery to whole mandibular explants and in vivo increased extracellular matrix deposition and increased cartilage thickness, while TNF-alpha treated explants had increased expression of inflammatory cytokines and degradative enzymes. Moreover, the application of TNF-alpha or CFA in both models reduced cell number. CFA delivery in vivo caused soft tissue inflammation, including pannus formation. Our work provides two methods of chemically induced TMJ inflammatory arthritis through a condyle explant model and intra-articular injection model that replicate findings seen in synovial fluid of human patients, which can be used for further studies delineating the mechanisms underlying TMJ pathology.
Asunto(s)
Artritis Experimental/inmunología , Cartílago Articular/inmunología , Matriz Extracelular/inmunología , Trastornos de la Articulación Temporomandibular/inmunología , Articulación Temporomandibular/inmunología , Proteína ADAMTS5/genética , Proteína ADAMTS5/inmunología , Adolescente , Adulto , Anciano , Animales , Artritis Experimental/inducido químicamente , Artritis Experimental/genética , Cartílago Articular/efectos de los fármacos , Cartílago Articular/patología , Colágeno Tipo II/genética , Colágeno Tipo II/inmunología , Colágeno Tipo X/genética , Colágeno Tipo X/inmunología , Modelos Animales de Enfermedad , Matriz Extracelular/efectos de los fármacos , Matriz Extracelular/patología , Femenino , Adyuvante de Freund/administración & dosificación , Expresión Génica/efectos de los fármacos , Expresión Génica/inmunología , Humanos , Interleucinas/genética , Interleucinas/inmunología , Masculino , Cóndilo Mandibular/efectos de los fármacos , Cóndilo Mandibular/inmunología , Cóndilo Mandibular/patología , Ratones , Ratones Endogámicos C57BL , Persona de Mediana Edad , Líquido Sinovial/inmunología , Articulación Temporomandibular/efectos de los fármacos , Articulación Temporomandibular/patología , Trastornos de la Articulación Temporomandibular/genética , Trastornos de la Articulación Temporomandibular/patología , Técnicas de Cultivo de Tejidos , Factor de Necrosis Tumoral alfa/administración & dosificaciónRESUMEN
Temporomandibular disorders (TMD) are a common stomatognathic disease affecting all age groups. Patients with internal derangement (ID) or osteoarthritis (OA) of temporomandibular joint (TMJ) often have TMJ synovitis. When TMJ synovial membrane is damaged, many inflammatory cytokines are produced and secreted from TMJ synoviocytes to synovial fluid of TMJ. It has been widely reported that many kinds of biologic factors are produced from TMJ synoviocytes stimulated with interleukin (IL)-1beta and tumor necrosis factor (TNF)-alpha. One of the major symptoms of TMD is pain of the TMJ. Many study groups have studied relations between the development of TMJ pain and biologic factors secreted into synovial fluid of TMJ. Here, we summarize previous reports trying to elucidate this correlation. On the other hand, it has been reported that a new molecular mechanism of IL-1beta secretion called inflammasome is involved in several diseases with sterile inflammation. Because TMJ synovitis with ID and OA of TMJ is also sterile inflammation, inflammasome may be involved in the development of TMJ synovial inflammation. This review describes some molecular mechanisms underlying inflammation in TMJ, especially in TMJ synovitis, which may be useful for the development of new therapies against TMD.
Asunto(s)
Trastornos de la Articulación Temporomandibular/inmunología , Animales , Citocinas/inmunología , Humanos , Dolor/inmunología , Membrana Sinovial/anatomía & histología , Membrana Sinovial/inmunología , Sinovitis/inmunología , Articulación Temporomandibular/anatomía & histología , Articulación Temporomandibular/inmunologíaRESUMEN
OBJECTIVES: Magnetic resonance imaging (MRI) is a standardized method for assisting joint diagnosis. To validate the reliability of different imaging-based grading systems, this study examined (1) the associations between grading systems for osseous change, joint effusion, and the Wilkes classification of temporomandibular joint (TMJ) disorders and (2) the correlation between cytokines in synovial fluid and imaging-based joint scores. MATERIALS AND METHODS: Twenty-seven patients, who routinely received numeric rating scale (NRS) and MRI assessment before TMJ arthrocentesis, were enrolled. Each joint was evaluated through the grading criteria for severity of osseous change and joint effusion by blinded observers using MRI. ImageJ was employed for classifying joint effusion. Joint synovial fluid, collected through arthrocentesis, was examined for cytokine expression by using a Luminex multiplex assay. All data were analyzed using the Pearson correlation analysis. RESULTS: The Wilkes classification was strongly correlated with osseous change scores, but not with joint effusion scores. Joint effusion scores significantly correlated with NRS scores, but not with the Wilkes classification and osseous change scores. Compared with osseous change scores, joint effusion scores had a higher correlation with the levels of inflammatory cytokines (interleukin (IL)-8 and soluble IL-6 receptor (sIL-6R)) and with anti-inflammatory cytokines (soluble tumor necrosis factor receptors I and II (sTNF-RI/II)). CONCLUSIONS: In patients with TMJ disorders, MRI grades are strongly correlated with NRS scores and levels of cytokines (IL-8, sIL-6R, and sTNF-RI/II) in the synovial fluid. CLINICAL RELEVANCE: Joint effusion scoring can be a reliable and valid indicator for pathological assessment of TMJ disorders.
Asunto(s)
Citocinas/análisis , Líquido Sinovial/química , Trastornos de la Articulación Temporomandibular/diagnóstico por imagen , Adulto , Anciano , Estudios Transversales , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Articulación Temporomandibular/diagnóstico por imagen , Articulación Temporomandibular/patología , Trastornos de la Articulación Temporomandibular/inmunología , Adulto JovenRESUMEN
Temporomandibular joint (TMJ) is frequently involved with rheumatoid arthritis with a high prevalence that could result in a chronic pain state. Once the disease is established in the joint, the antigen-specific immune reaction initiates a neuro-immune cascade of events that causes sensitization of the central nervous system. This study establishes animal experimental models that evaluate the chronicity of albumin-induced arthritis hypernociception in the TMJ. Antigen-induced arthritis was generated in rats with methylated bovine serum albumin (mBSA) diluted in complete Freund's. Intra-articular injection of mBSA (10⯵g/TMJ/week) during 3â¯weeks resulted in a persistent inflammatory hypernociception which was characterized by an inflammatory episode characterized by the increased of lymphocytes, macrophages and pro-inflammatory interleukins IL-12 and IL-18. The persistent model of inflammatory hypernociception induced by arthritis in the TMJ elicited protein levels of P2X7 receptors, cathepsin S and fractalkine in the trigeminal subnucleus caudalis. Overall, the results of the present work suggest that a persistent inflammatory hypernociception of albumin-induced arthritis in the TMJ leads to the activation of the central nervous system signaling by P2X7/cathepsin S/fractalkine pathway.
Asunto(s)
Artritis/metabolismo , Catepsinas/metabolismo , Quimiocina CX3CL1/metabolismo , Nocicepción , Receptores Purinérgicos P2X7/metabolismo , Trastornos de la Articulación Temporomandibular/metabolismo , Núcleos del Trigémino/metabolismo , Animales , Artritis/complicaciones , Artritis/inmunología , Artritis Experimental/inducido químicamente , Modelos Animales de Enfermedad , Masculino , Ratas Wistar , Albúmina Sérica Bovina/administración & dosificación , Transducción de Señal , Trastornos de la Articulación Temporomandibular/complicaciones , Trastornos de la Articulación Temporomandibular/inmunología , Núcleos del Trigémino/inmunologíaRESUMEN
It is well accepted that the presence of cytokines belonging to the Th1/Th17/Th22 axis of immuno-inflammatory response in the joint environment, such as IL-1ß, IL-17 and IL-22, respectively, are associated with pathogenesis of several synovial joint degenerative disorders. During temporomandibular joint osteoarthritis (TMJ-OA), IL-1ß and IL-17 have been implicated in the inflammation and resorption of sub-chondral bone; however, the role of Th22 response in the TMJ-OA pathophysiology has not been established. This study aimed to compare the expression of Th1/Th17/Th22-type cytokines, chemokines and chemokine receptors in synovial fluid samples obtained from TMJ-OA or disk displacement with reduction (DDWR) patients. In addition, it aimed to associate these levels with joint pain, imagenological signs of bone degeneration, RANKL production, osteoclastogenesis and osteoclast-induced bone resorption. Higher levels of IL-1ß, IL-17 and IL-22 were expressed in TMJ-OA compared with DDWR subjects, and these increased levels significantly correlated with RANKL expression, joint pain and articular bone degeneration. Higher levels of CCR5, CCR6 and CCR7, as well as their respective ligands CCL5 and CCL20, responsible for recruitment of IL-1ß, IL-17 and IL-22-producing cells, were over-expressed in TMJ-OA compared with DDWR subjects. Osteoclastogenesis and osteoclast-induced bone resorption were significantly greater in presence of synovial fluid from TMJ-OA compared with DDWR subjects. These data demonstrate that cytokines, CCLs and CCRs associated with the Th1/Th17/Th22 axis of immuno-inflammatory response are involved in TMJ-OA pathogenesis. These findings suggest that IL-22 is involved in the RANKL expression in TMJ-OA, which in turn induces differentiation of osteoclasts and subsequent resorption of sub-chondral bone.
Asunto(s)
Osteoartritis/inmunología , Osteoclastos/metabolismo , Ligando RANK/metabolismo , Líquido Sinovial/citología , Linfocitos T Colaboradores-Inductores/metabolismo , Trastornos de la Articulación Temporomandibular/inmunología , Articulación Temporomandibular/patología , Adulto , Anciano , Resorción Ósea , Diferenciación Celular , Células Cultivadas , Femenino , Humanos , Masculino , Persona de Mediana Edad , Osteoartritis/fisiopatología , Subgrupos de Linfocitos T , Trastornos de la Articulación Temporomandibular/fisiopatología , Adulto JovenRESUMEN
Evidence-based clinical diagnostic criteria for temporomandibular joint (TMJ) arthritis are not available. To establish (i) criteria for clinical diagnosis of TMJ arthritis and (ii) clinical variables useful to determine inflammatory activity in TMJ arthritis using synovial fluid levels of inflammatory mediators as the reference standard. A calibrated examiner assessed TMJ pain, function, noise and occlusal changes in 219 TMJs (141 patients, 15 healthy individuals). TMJ synovial fluid samples were obtained with a push-pull technique using the hydroxycobalamin method and analysed for TNF, TNFsRII, IL-1ß, IL-1ra, IL-1sRII, IL-6 and serotonin. If any inflammatory mediator concentration exceeded normal, the TMJ was considered as arthritic. In the patient group, 71% of the joints were arthritic. Of those, 93% were painful. About 66% of the non-arthritic TMJs were painful to some degree. Intensity of TMJ resting pain and TMJ maximum opening pain, number of jaw movements causing TMJ pain and laterotrusive movement to the contralateral side significantly explained presence of arthritis (AUC 0.72, P < .001). Based on these findings, criteria for possible, probable and definite TMJ arthritis were determined. Arthritic TMJs with high inflammatory activity showed higher pain intensity on maximum mouth opening (P < .001) and higher number of painful mandibular movements (P = .004) than TMJs with low inflammatory activity. The combination TMJ pain on maximum mouth opening and Contralateral laterotrusion <8 mm appears to have diagnostic value for TMJ arthritis. Among arthritic TMJs, higher TMJ pain intensity on maximum mouth opening and number of mandibular movements causing TMJ pain indicates higher inflammatory activity.
Asunto(s)
Artritis Reumatoide/diagnóstico , Dolor Facial/diagnóstico , Trastornos de la Articulación Temporomandibular/diagnóstico , Adulto , Artritis Reumatoide/inmunología , Citocinas/metabolismo , Progresión de la Enfermedad , Dolor Facial/fisiopatología , Femenino , Humanos , Masculino , Estándares de Referencia , Líquido Sinovial/inmunología , Trastornos de la Articulación Temporomandibular/inmunología , Trastornos de la Articulación Temporomandibular/fisiopatologíaRESUMEN
A rapidly increasing number of mandibular condylar fractures and some complications related to injuries of temporomandibular elements make this study important. Intra-articular disorders lead to secondary pathological findings such as osteoarthritis, deforming osteoarthrosis, and temporomandibular joint ankylosis that limits mouth opening, mastication, swallowing, breathing, and decreased/lost working capacity or disability. Early diagnosis of intra-articular disorders can prevent from long-lasting functional complications caused by temporomandibular joint injuries. This study was performed for the purpose of early detection and investigation of organic pathological changes in the cartilaginous and osseous tissues of the temporomandibular joint caused by traumatic fractures of the mandibular condyle. Twenty patients underwent a general clinical examination, magnetic resonance imaging (MRI), and immune-enzyme testing for biochemical markers of connective tissue injury (pyridinoline and deoxypyridinoline) in urine. Disk dislocation, deformation, adhesion, perforation or squeeze, tension or disruption of ligaments, and injury of articular surfaces are among complications of mandibular fractures that can be revealed on MRI. As regards biochemical findings, we revealed a sharp rise in the levels of pyridinoline and deoxypyridinoline before treatment and a lack of stabilization within 21 days of treatment.
Asunto(s)
Fracturas Mandibulares/inmunología , Fracturas Mandibulares/patología , Trastornos de la Articulación Temporomandibular/inmunología , Trastornos de la Articulación Temporomandibular/patología , Diagnóstico Precoz , Femenino , Humanos , Técnicas para Inmunoenzimas , Imagen por Resonancia Magnética , MasculinoRESUMEN
Temporomandibular disorders (TMD) are a set of conditions characterized by pain and dysfunction in the temporomandibular joint and muscles of mastication. These pain conditions are associated with considerable morbidity, societal costs, and reduced quality of life. The prevalence varies between 4% and 10%, with females at higher risk, and a higher prevalence occurs during reproductive years. The increased prevalence of TMD in females and low prevalence in childhood reinforce that sex hormones, like estrogen, play an important, complex role in the pathophysiology of these disorders. The goal of this study was to determine whether women with TMD exhibit a monocytic hyperinflammatory response compared with control women, and to examine associations of monocytic inflammatory responses with clinical pain. Eighteen women, aged 18 to 35 y, were seen during their follicular menstrual phase. A blood sample was collected, a clinical questionnaire about pain history was administered, and a Research Diagnostic Criteria (RDC) exam was performed. Extracted monocytes were stimulated with the toll-like receptor (TLR)-4 ligand, lipopolysaccharide (LPS), in the presence and absence of estrogen, and the levels of IL6 expression evaluated. Women with TMD showed a systemic hyperinflammatory phenotype, manifested by an increased monocytic release of cytokines after an inflammatory insult, and this was further increased by estrogen. In addition, monocytes from participants who self-reported more pain on the VAS scale produced higher levels of IL6 compared with those from participants who self-reported lower pain sensitivity. These data suggest that an estrogen-induced hyperinflammatory phenotype in women with TMD may at least in part contribute to heightened clinical pain, perhaps via central sensitization.
Asunto(s)
Artralgia/inmunología , Artralgia/fisiopatología , Estrógenos/farmacología , Dolor Facial/inmunología , Dolor Facial/fisiopatología , Monocitos/inmunología , Trastornos de la Articulación Temporomandibular/inmunología , Trastornos de la Articulación Temporomandibular/fisiopatología , Adolescente , Adulto , Estudios de Casos y Controles , Femenino , Fase Folicular , Humanos , Interleucina-6/sangre , Lipopolisacáridos , Dimensión del Dolor , Fenotipo , Encuestas y Cuestionarios , Receptor Toll-Like 4/sangreRESUMEN
The aim of this study was to find out if reactive arthritis was involved in the aetiology of chronic closed lock of the temporomandibular joint (TMJ) by looking for bacterial antigens in the synovial membrane of the TMJ, and by studying the antibody serology and carriage of human leucocyte antigen (HLA) B27 in patients with chronic closed lock. Patients with reciprocal clicking and healthy subjects acted as controls. We studied a total of 43 consecutive patients, 15 with chronic closed lock, 13 with reciprocal clicking, and 15 healthy controls with no internal derangements of the TMJ. Venous blood samples were collected from all subjects for measurement of concentrations of HLA tissue antigen and serology against Chlamydia trachomatis, Yersinia enterocolitica, Salmonella spp., Campylobacter jejuni, and Mycoplasma pneumoniae. Samples of synovial tissue from patients with closed lock and reciprocal clicking were obtained during discectomy and divided into two pieces, the first of which was tested by strand displacement amplification for the presence of C trachomatis, and the second of which was analysed for the presence of species-specific bacterial DNA using 16s rRNA pan-polymerase chain reaction (PCR). There were no significant differences between the groups in the incidence of antibodies against M pneumoniae, Salmonella spp. or Y enterocolitica. No patient had antibodies towards C trachomatis or C jejuni. We found no bacterial DNA in the synovial fluid from any patient. The HLA B27 antigen was present in 2/15 subjects in both the closed lock and control groups, and none in the reciprocal clicking group. In conclusion, reactive arthritis does not seem to be the mechanism of internal derangement of the TMJ.
Asunto(s)
Artritis Reactiva/microbiología , Luxaciones Articulares/microbiología , Trastornos de la Articulación Temporomandibular/microbiología , Adulto , Anciano , Anticuerpos Antibacterianos/sangre , Antígenos Bacterianos/análisis , Artritis Reactiva/genética , Campylobacter jejuni/genética , Campylobacter jejuni/inmunología , Estudios de Casos y Controles , Chlamydia trachomatis/genética , Chlamydia trachomatis/inmunología , ADN Bacteriano/análisis , Femenino , Antígeno HLA-B27/análisis , Humanos , Inmunoglobulina G/sangre , Inmunoglobulina M/sangre , Luxaciones Articulares/inmunología , Masculino , Persona de Mediana Edad , Mycoplasma pneumoniae/genética , Mycoplasma pneumoniae/inmunología , Dimensión del Dolor/métodos , Rango del Movimiento Articular/fisiología , Salmonella/genética , Salmonella/inmunología , Membrana Sinovial/inmunología , Trastornos de la Articulación Temporomandibular/inmunología , Yersinia enterocolitica/genética , Yersinia enterocolitica/inmunología , Adulto JovenRESUMEN
The aim was to investigate how endogenous cytokine control of tumor necrosis factor (TNF) influences temporomandibular joint (TMJ) pain in relation to the role of anti-citrullinated peptide antibodies (ACPA) in patients with rheumatoid arthritis (RA). Twenty-six consecutive patients with TMJ RA were included. Temporomandibular joint pain intensity was assessed at rest, on maximum mouth opening, on chewing, and on palpation. Mandibular movement capacity and degree of anterior open bite (a clinical sign of structural destruction of TMJ tissues) were also assessed. Systemic inflammatory activity was assessed using the Disease Activity Score in 28 joints (DAS28) for rheumatoid arthritis. Samples of TMJ synovial fluid and blood were obtained and analyzed for TNF, its soluble receptor, soluble TNF receptor II (TNFsRII), and ACPA. A high concentration of TNF in relation to the concentration of TNFsRII in TMJ synovial fluid was associated with TMJ pain on posterior palpation on maximum mouth opening. The ACPA concentration correlated significantly to the TNF concentration, but not to the TNFsRII concentration, indicating that increased inflammatory activity is mainly caused by an insufficient increase in anti-inflammatory mediators. This study indicates that TMJ pain on palpation in patients with RA is related to a deficiency in local cytokine control that contributes to increased inflammatory activity, including sensitization to mechanical stimuli over the TMJ.
Asunto(s)
Artritis Reumatoide/inmunología , Interleucina-1beta/inmunología , Trastornos de la Articulación Temporomandibular/inmunología , Factor de Necrosis Tumoral alfa/inmunología , Adulto , Autoanticuerpos/análisis , Autoanticuerpos/sangre , Sedimentación Sanguínea , Proteína C-Reactiva/análisis , Femenino , Humanos , Proteína Antagonista del Receptor de Interleucina 1/análisis , Proteína Antagonista del Receptor de Interleucina 1/sangre , Interleucina-1beta/análisis , Interleucina-1beta/sangre , Masculino , Masticación/fisiología , Persona de Mediana Edad , Mordida Abierta/clasificación , Dimensión del Dolor/métodos , Palpación , Péptidos Cíclicos/análisis , Péptidos Cíclicos/sangre , Rango del Movimiento Articular/fisiología , Receptores Tipo I de Interleucina-1/análisis , Receptores Tipo I de Interleucina-1/sangre , Receptores Tipo II de Interleucina-1/análisis , Receptores Tipo II de Interleucina-1/sangre , Receptores Tipo II del Factor de Necrosis Tumoral/análisis , Receptores Tipo II del Factor de Necrosis Tumoral/sangre , Factor Reumatoide/análisis , Factor Reumatoide/sangre , Líquido Sinovial/química , Factor de Necrosis Tumoral alfa/análisis , Factor de Necrosis Tumoral alfa/sangreRESUMEN
OBJECTIVE: To investigate if TNF, IL-1 or their endogenous controls, in relation to ACPA, are associated with radiological signs of ongoing temporomandibular joint (TMJ) bone tissue resorption and disc displacement in RA patients. METHODS: Twenty-two consecutive outpatients with TMJ of RA were included. Systemic inflammatory activity was assessed by DAS28. The number of painful regions in the body and ESR, CRP, RF and ACPA were analyzed. TMJ synovial fluid and blood samples were obtained and analyzed for TNF, TNFsRII, IL-1ra, IL-1sRII and ACPA. The ratios between the mediators and their endogenous control receptors were used in the statistical analysis. Magnetic resonance imaging was performed in closed- and open-mouth positions and evaluated regarding disc position and presence of condylar and temporal erosions of the TMJ. RESULTS: A high TNF level in relation to TNFsRII in TMJ synovial fluid correlated to the degree of TMJ condylar erosion. A high IL-1ra level in relation to TNF in TMJ synovial fluid was also correlated to the degree of TMJ condylar erosion. The total degree of TMJ condylar erosion was correlated with the number of painful regions. CONCLUSION: This study indicates that TNF in TMJ synovial fluid mediates TMJ cartilage and bone tissue resorption in RA. The study also suggests that the degree of endogenous cytokine control is of importance for development of bone tissue destruction.
Asunto(s)
Artritis Reumatoide/inmunología , Trastornos de la Articulación Temporomandibular/inmunología , Articulación Temporomandibular/inmunología , Factor de Necrosis Tumoral alfa/inmunología , Adulto , Artritis Reumatoide/patología , Autoanticuerpos/análisis , Sedimentación Sanguínea , Resorción Ósea/inmunología , Proteína C-Reactiva/análisis , Cartílago Articular/inmunología , Femenino , Humanos , Proteína Antagonista del Receptor de Interleucina 1/análisis , Interleucina-1beta/análisis , Luxaciones Articulares/inmunología , Imagen por Resonancia Magnética/métodos , Masculino , Cóndilo Mandibular/inmunología , Persona de Mediana Edad , Dolor/inmunología , Receptores Tipo II de Interleucina-1/análisis , Receptores Tipo II del Factor de Necrosis Tumoral/análisis , Líquido Sinovial/inmunología , Articulación Temporomandibular/patología , Disco de la Articulación Temporomandibular/inmunología , Trastornos de la Articulación Temporomandibular/patologíaRESUMEN
The aim of this study was to evaluate the peripheral effect of 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) in albumin-induced arthritis in temporomandibular joint (TMJ) of rats. Antigen-induced arthritis (AIA) was generated in rats with methylated bovine serum albumin (mBSA) diluted in complete Freund׳s adjuvant. Pretreatment with an intra-articular injection of 15d-PGJ2 (100 ng/TMJ) before mBSA intra-articular injection (10 µg/TMJ) (challenge) in immunized rats significantly reduced the albumin-induced arthritis inflammation. The results demonstrated that 15d-PGJ2 was able to inhibit plasma extravasation, leukocyte migration and the release of inflammatory cytokines IL-6, IL-12, IL-18 and the chemokine CINC-1 in the TMJ tissues. In addition, 15d-PGJ2 was able to increase the expression of the anti-adhesive molecule CD55 and the anti-inflammatory cytokine IL-10. Taken together, it is possible to suggest that 15d-PGJ2 inhibit leukocyte infiltration and subsequently inflammatory process, through a shift in the balance of the pro- and anti-adhesive properties. Thus, 15d-PGJ2 might be used as a potential anti-inflammatory drug to treat arthritis-induced inflammation of the temporomandibular joint.
Asunto(s)
Antiinflamatorios/uso terapéutico , Artritis Experimental/tratamiento farmacológico , Prostaglandina D2/análogos & derivados , Trastornos de la Articulación Temporomandibular/tratamiento farmacológico , Animales , Antiinflamatorios/farmacología , Antígenos , Artritis Experimental/inmunología , Antígenos CD55/inmunología , Movimiento Celular/efectos de los fármacos , Citocinas/inmunología , Adyuvante de Freund , Inyecciones Intraarticulares , Molécula 1 de Adhesión Intercelular/inmunología , Leucocitos/efectos de los fármacos , Leucocitos/fisiología , Masculino , Prostaglandina D2/farmacología , Prostaglandina D2/uso terapéutico , Ratas Wistar , Albúmina Sérica Bovina , Trastornos de la Articulación Temporomandibular/inmunologíaRESUMEN
AIM: A study was performed on the articular disk and periarticular tissues of the temporo-mandibular joint (TMJ) with immunohistochemical techniques to give evidence to the presence of neuroreceptors (NRec) in these sites. METHODS: The study was carried out on tissue samples obtained from 10 subjects without TMJ disease and from 7 patients with severe TMJ arthritis and arthrosis. We use antibodies directed against following antigens: Gliofibrillary Acidic Protein (GFAP), Leu-7, Myelin Basic Protein (MBP), Neurofilaments 68 kD (NF), Neuron Specific Enolase (NSE), S-100 protein (S-100) and Synaptophysin (SYN). RESULTS: This study revealed that Ruffini's-like, Pacini's-like and Golgi's-like receptors can be demonstrated in TMJ periarticular tissues and that free nervous endings are present in the subsynovial tissues but not within the articular disk. We observed elongated cytoplamic processes of chondrocytes that demonstrated strong S-100 immunoreactivity but they were unreactive with all other antibodies. These cytoplamic processes were more abundant and thicker in the samples obtained from patients with disease TMJ. CONCLUSION: The results of this study confirm that different Nrec are detectable in TMJ periarticular tissues but they are absent within the articular disk. In the latter site, only condrocytic processes are evident, especially in diseased TMJ, and they might have been confused with nervous endings in previous morphological studies. Nevertheless the absence of immunoreactivity for NF, NSE and SYN proves that they are not of neural origin.
Asunto(s)
Células Receptoras Sensoriales/metabolismo , Trastornos de la Articulación Temporomandibular/metabolismo , Trastornos de la Articulación Temporomandibular/patología , Articulación Temporomandibular/metabolismo , Articulación Temporomandibular/patología , Adulto , Anticuerpos/inmunología , Condrocitos/inmunología , Condrocitos/metabolismo , Condrocitos/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proteína Básica de Mielina/inmunología , Proteína Básica de Mielina/aislamiento & purificación , Proteína Básica de Mielina/metabolismo , Proteínas de Neurofilamentos/inmunología , Proteínas de Neurofilamentos/aislamiento & purificación , Proteínas de Neurofilamentos/metabolismo , Fosfopiruvato Hidratasa/inmunología , Fosfopiruvato Hidratasa/aislamiento & purificación , Fosfopiruvato Hidratasa/metabolismo , Proteínas S100/inmunología , Proteínas S100/aislamiento & purificación , Proteínas S100/metabolismo , Células Receptoras Sensoriales/inmunología , Sinaptofisina/inmunología , Sinaptofisina/aislamiento & purificación , Sinaptofisina/metabolismo , Articulación Temporomandibular/inmunología , Trastornos de la Articulación Temporomandibular/inmunologíaRESUMEN
OBJECTIVES: ß-defensin-4 is a member of antimicrobial peptides (APs) of the immunity system. This molecule has antimicrobial activity but it seems to be involved in articular inflammatory processes too, as it happens during osteoarthritic disease (OA). Considering the possible relation existing between (OA) and temporomandibular disorders (TMD), the aim of our study was to evaluate immunohistochemically the presence of ß- defensin-4 in pathological temporomandibular joint (TMJ) discs affected by internal derangement without reduction (ADDwoR). DESIGN: Eighteen TMJ-displaced disc specimens were considered in this study and were analysed by immunohistochemical evaluation. They were compared with a control sample of sixteen healthy discs and two scores, intensity of staining (IS) and extent score (ES) were estimated. RESULTS: Findings of our analysis showed a significant difference between control and study sample (P < 0.001). IS and ES of control sample and pathological sample were 1 and 4 respectively. CONCLUSION: Our results confirmed the presence of ß-defensin-4 in human TMJ discs affected by ADDwoR, hypothesing a possible role of this molecule in articular bone disruption.