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1.
Proc Natl Acad Sci U S A ; 121(8): e2306132121, 2024 Feb 20.
Artículo en Inglés | MEDLINE | ID: mdl-38346188

RESUMEN

Temporomandibular joint osteoarthritis (TMJ OA) is a prevalent degenerative disease characterized by chronic pain and impaired jaw function. The complexity of TMJ OA has hindered the development of prognostic tools, posing a significant challenge in timely, patient-specific management. Addressing this gap, our research employs a comprehensive, multidimensional approach to advance TMJ OA prognostication. We conducted a prospective study with 106 subjects, 74 of whom were followed up after 2 to 3 y of conservative treatment. Central to our methodology is the development of an innovative, open-source predictive modeling framework, the Ensemble via Hierarchical Predictions through Nested cross-validation tool (EHPN). This framework synergistically integrates 18 feature selection, statistical, and machine learning methods to yield an accuracy of 0.87, with an area under the ROC curve of 0.72 and an F1 score of 0.82. Our study, beyond technical advancements, emphasizes the global impact of TMJ OA, recognizing its unique demographic occurrence. We highlight key factors influencing TMJ OA progression. Using SHAP analysis, we identified personalized prognostic predictors: lower values of headache, lower back pain, restless sleep, condyle high gray level-GL-run emphasis, articular fossa GL nonuniformity, and long-run low GL emphasis; and higher values of superior joint space, mouth opening, saliva Vascular-endothelium-growth-factor, Matrix-metalloproteinase-7, serum Epithelial-neutrophil-activating-peptide, and age indicate recovery likelihood. Our multidimensional and multimodal EHPN tool enhances clinicians' decision-making, offering a transformative translational infrastructure. The EHPN model stands as a significant contribution to precision medicine, offering a paradigm shift in the management of temporomandibular disorders and potentially influencing broader applications in personalized healthcare.


Asunto(s)
Osteoartritis , Trastornos de la Articulación Temporomandibular , Humanos , Estudios Prospectivos , Articulación Temporomandibular , Osteoartritis/terapia , Trastornos de la Articulación Temporomandibular/terapia , Proyectos de Investigación
2.
Biol Cell ; 116(1): e202300042, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37919852

RESUMEN

BGROUND INFORMATION: Ferroptosis contributes to temporomandibular joint osteoarthritis (TMJOA) lesion development and is still poorly understood. RESULTS: 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-1ß, 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-1ß 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-1ß. CONCLUSION: These results suggest that chondrocyte ferroptosis plays an important role in the development and progression of TMJOA. SIGNIFICANCE: Inhibiting condylar chondrocyte ferroptosis could be a promising therapeutic strategy for TMJOA.


Asunto(s)
Cartílago Articular , Ferroptosis , Quinoxalinas , Compuestos de Espiro , Ratas , Animales , Condrocitos/metabolismo , Condrocitos/patología , Proteína p53 Supresora de Tumor/metabolismo , Proteína p53 Supresora de Tumor/farmacología , Ratas Sprague-Dawley , Cartílago Articular/metabolismo , Cartílago Articular/patología , Articulación Temporomandibular/metabolismo , Articulación Temporomandibular/patología
3.
J Cell Mol Med ; 28(11): e18472, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38842129

RESUMEN

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


Asunto(s)
Apoptosis , Calcio , Condrocitos , Estrés del Retículo Endoplásmico , Canales Iónicos , Osteoartritis , Articulación Temporomandibular , Condrocitos/metabolismo , Condrocitos/patología , Canales Iónicos/metabolismo , Canales Iónicos/genética , Animales , Articulación Temporomandibular/metabolismo , Articulación Temporomandibular/patología , Calcio/metabolismo , Osteoartritis/metabolismo , Osteoartritis/patología , Humanos , Ratones , Transducción de Señal , Venenos de Araña , Péptidos y Proteínas de Señalización Intercelular
4.
J Cell Mol Med ; 28(7): e18172, 2024 04.
Artículo en Inglés | MEDLINE | ID: mdl-38494837

RESUMEN

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.


Asunto(s)
Osteoartritis , Sinovitis , Humanos , Animales , Ratones , Ácido Hialurónico , Sinovitis/patología , Articulación Temporomandibular/patología , Inflamación/patología , Osteoartritis/metabolismo , Macrófagos/metabolismo , Proteínas Quinasas
5.
Biochem Biophys Res Commun ; 726: 150278, 2024 Sep 24.
Artículo en Inglés | MEDLINE | ID: mdl-38936248

RESUMEN

Temporomandibular joint (TMJ) disorder (TMD) is a chronic progressive disease that is commonly seen in clinical settings. TMJ disc degeneration is an important manifestation of TMD, and further aggravates the progression of TMD. However, treatments on TMJ disc degeneration are very limited till now. In this study, we first observed the effects of bone marrow stem cells (BMSC) conditioned medium on functions of TMJ disc fibroblasts. Then BMSC-derived small extracellular vesicles (BMSC-EVs) were isolated and exposed to TMJ disc fibroblasts. RNA-sequencing was used to further investigate the mechanisms. BMSC-EVs were finally injected into a rat model with TMD. Results showed that in the transwell co-culture system, the medium derived from BMSC reduced inflammation and enhanced chondrogenesis in TMJ disc fibroblasts. BMSC-EVs promoted proliferation, migration, and chondrogenic differentiation of TMJ disc fibroblasts, and inhibited apoptosis and inflammatory responses. Local injection of BMSC-EVs into the TMD model alleviated TMJ disc degeneration. Therefore, BMSC-EVs were a potentially effective, sustainable and clinically translational-promising option for TMJ disc degeneration, and further reduce the progression of TMD.


Asunto(s)
Exosomas , Células Madre Mesenquimatosas , Ratas Sprague-Dawley , Disco de la Articulación Temporomandibular , Trastornos de la Articulación Temporomandibular , Animales , Células Madre Mesenquimatosas/metabolismo , Células Madre Mesenquimatosas/citología , Exosomas/metabolismo , Exosomas/trasplante , Trastornos de la Articulación Temporomandibular/terapia , Trastornos de la Articulación Temporomandibular/patología , Trastornos de la Articulación Temporomandibular/metabolismo , Ratas , Disco de la Articulación Temporomandibular/patología , Disco de la Articulación Temporomandibular/metabolismo , Fibroblastos/metabolismo , Fibroblastos/patología , Masculino , Medios de Cultivo Condicionados/farmacología , Células Cultivadas , Condrogénesis , Modelos Animales de Enfermedad , Humanos , Diferenciación Celular , Proliferación Celular
6.
J Neurosci Res ; 102(1): e25269, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-38284851

RESUMEN

This study aimed to evaluate the effects of inhibitors of the fractalkine pathway in hyperalgesia in inflammatory and neuropathic orofacial pain in male rats and the morphological changes in microglia and satellite glial cells (SGCs). Rats were submitted to zymosan-induced arthritis of the temporomandibular joint or infraorbital nerve constriction, and treated intrathecally with a P2 X7 antagonist, a cathepsin S inhibitor or a p-38 mitogen-activated protein kinase (MAPK) inhibitor. Mechanical hyperalgesia was evaluated 4 and 6 h following arthritis induction or 7 and 14 days following nerve ligation. The expression of the receptor CX3 CR1 , phospho-p-38 MAPK, ionized calcium-binding adapter molecule-1 (Iba-1), and glutamine synthetase and the morphological changes in microglia and SGCs were evaluated by confocal microscopy. In both inflammatory and neuropathic models, untreated animals presented a higher expression of CX3 CR1 and developed hyperalgesia and up-regulation of phospho-p-38 MAPK, which was prevented by all drugs (p < .05). The number of microglial processes endpoints and the total branch length were lower in the untreated animals, but the overall immunolabeling of Iba-1 was altered only in neuropathic rats (p < .05). The mean area of SGCs per neuron was significantly altered only in the inflammatory model (p < .05). All morphological alterations were reverted by modulating the fractalkine pathway (p < .05). In conclusion, the blockage of the fractalkine pathway seemed to be a possible therapeutic strategy for inflammatory and neuropathic orofacial pain, reducing mechanical hyperalgesia by impairing the phosphorylation of p-38 MAPK and reverting morphological alterations in microglia and SGCs.


Asunto(s)
Artritis , Neuralgia , Masculino , Animales , Ratas , Hiperalgesia/tratamiento farmacológico , Quimiocina CX3CL1 , Neuroglía , Neuralgia/tratamiento farmacológico , Proteínas Quinasas Activadas por Mitógenos , Inhibidores de Proteínas Quinasas , Dolor Facial/tratamiento farmacológico , Proteínas Quinasas p38 Activadas por Mitógenos
7.
J Transl Med ; 22(1): 662, 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-39010104

RESUMEN

BACKGROUND: Temporomandibular joint osteoarthritis (TMJOA) has a high incidence rate, but its pathogenesis remains unclear. Circadian rhythm is an important oscillation in the human body and influences various biological activities. However, it is still unclear whether circadian rhythm affects the onset and development of TMJOA. METHODS: We disrupted the normal rhythm of rats and examined the expression of core clock genes in the mandibular condylar cartilage of the jaw and histological changes in condyles. After isolating rat mandibular condylar chondrocytes, we upregulated or downregulated the clock gene Per1, examined the expression of cartilage matrix-degrading enzymes, tested the activation of the GSK3ß/ß-CATENIN pathway and verified it using agonists and inhibitors. Finally, after downregulating the expression of Per1 in the mandibular condylar cartilage of rats with jet lag, we examined the expression of cartilage matrix-degrading enzymes and histological changes in condyles. RESULTS: Jet lag led to TMJOA-like lesions in the rat mandibular condyles, and the expression of the clock gene Per1 and cartilage matrix-degrading enzymes increased in the condylar cartilage of rats. When Per1 was downregulated or upregulated in mandibular condylar chondrocytes, the GSK3ß/ß-CATENIN pathway was inhibited or activated, and the expression of cartilage matrix-degrading enzymes decreased or increased, which can be rescued by activator and inhibitor of the GSK3ß/ß-CATENIN pathway. Moreover, after down-regulation of Per1 in mandibular condylar cartilage in vivo, significant alleviation of cartilage degradation, cartilage loss, subchondral bone loss induced by jet lag, and inhibition of the GSK3ß/ß-CATENIN signaling pathway were observed. Circadian rhythm disruption can lead to TMJOA. The clock gene Per1 can promote the occurrence of TMJOA by activating the GSK3ß/ß-CATENIN pathway and promoting the expression of cartilage matrix-degrading enzymes. The clock gene Per1 is a target for the prevention and treatment of TMJOA.


Asunto(s)
Condrocitos , Ritmo Circadiano , Glucógeno Sintasa Quinasa 3 beta , Cóndilo Mandibular , Osteoartritis , Proteínas Circadianas Period , Articulación Temporomandibular , Regulación hacia Arriba , beta Catenina , Animales , Glucógeno Sintasa Quinasa 3 beta/metabolismo , Condrocitos/metabolismo , Condrocitos/patología , beta Catenina/metabolismo , Osteoartritis/patología , Osteoartritis/metabolismo , Proteínas Circadianas Period/metabolismo , Proteínas Circadianas Period/genética , Cóndilo Mandibular/patología , Cóndilo Mandibular/metabolismo , Articulación Temporomandibular/patología , Articulación Temporomandibular/metabolismo , Masculino , Ratas Sprague-Dawley , Transducción de Señal , Ratas
8.
Osteoarthritis Cartilage ; 32(6): 666-679, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38403153

RESUMEN

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


Asunto(s)
Condrocitos , Cóndilo Mandibular , MicroARNs , FN-kappa B , Receptor Toll-Like 4 , Animales , Femenino , Ratones , Ratas , Cartílago Articular/metabolismo , Cartílago Articular/patología , Senescencia Celular/genética , Condrocitos/metabolismo , Cóndilo Mandibular/patología , Ratones Endogámicos C57BL , MicroARNs/genética , FN-kappa B/metabolismo , Osteoartritis/genética , Osteoartritis/metabolismo , Osteoartritis/patología , Ratas Sprague-Dawley , Transducción de Señal , Articulación Temporomandibular/patología , Articulación Temporomandibular/metabolismo , Receptor Toll-Like 4/genética , Receptor Toll-Like 4/metabolismo
9.
Cell Mol Neurobiol ; 44(1): 22, 2024 Feb 16.
Artículo en Inglés | MEDLINE | ID: mdl-38363424

RESUMEN

Calcitonin gene-related peptide (CGRP) is synthesized and secreted by trigeminal ganglion neurons, and is a key neuropeptide involved in pain and immune regulation. This study investigates the expression of CGRP in the trigeminal ganglion (TG) and its regulatory role in the polarization of macrophages in rats with temporomandibular arthritis. A rat model of temporomandibular arthritis was established using CFA. Pain behavior was then observed. Temporomandibular joint (TMJ) and the TG were collected, and immunohistochemistry, immunofluorescence (IF) staining, and RT-qPCR were used to examine the expression of CGRP and macrophage-related factors. To investigate the impact of CGRP on macrophage polarization, both CGRP and its antagonist, CGRP 8-37, were separately administered directly within the TG. Statistical analysis revealed that within 24 h of inducing temporomandibular arthritis using CFA, there was a significant surge in CD86 positive macrophages within the ganglion. These macrophages peaked on the 7th day before beginning their decline. In this context, it's noteworthy that administering CGRP to the trigeminal ganglion can prompt these macrophages to adopt the M2 phenotype. Intriguingly, this study demonstrates that injecting the CGRP receptor antagonist (CGRP 8-37) to the ganglion counteracts this shift towards the M2 phenotype. Supporting these in vivo observations, we found that in vitro, CGRP indeed fosters the M2-type polarization of macrophages. CGRP can facilitate the conversion of macrophages into the M2 phenotype. The phenotypic alterations of macrophages within the TG could be instrumental in initiating and further driving the progression of TMJ disorders.


Asunto(s)
Péptido Relacionado con Gen de Calcitonina , Macrófagos , Trastornos de la Articulación Temporomandibular , Ganglio del Trigémino , Animales , Ratas , Péptido Relacionado con Gen de Calcitonina/metabolismo , Macrófagos/metabolismo , Dolor/metabolismo , Trastornos de la Articulación Temporomandibular/metabolismo , Ganglio del Trigémino/metabolismo
10.
FASEB J ; 37(8): e23004, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37440279

RESUMEN

The superficial zone cells in mandibular condylar cartilage are proliferative. The present purpose was to delineate the relation of calcium-sensing receptor (CaSR) and parathyroid hormone-related peptide nuclear localization sequence (PTHrP87-139 ), and their role in the proliferation behaviors of the superficial zone cells. A gain- and loss-of-function strategy were used in an in vitro fluid flow shear stress (FFSS) model and an in vivo bilateral elevation bite model which showed mandibular condylar cartilage thickening. CaSR and PTHrP87-139 were modulated through treating the isolated superficial zone cells with activator/SiRNA and via deleting CaSR or parathyroid hormone-related peptide (PTHrP) gene in mice with the promoter gene of proteoglycan 4 (Prg4-CreERT2 ) in the tamoxifen-inducible pattern with or without additional injection of Cinacalcet, the CaSR agonist, or PTHrP87-139 peptide. FFSS stimulated CaSR and PTHrP expression, and accelerated proliferation of the Prg4-expressing superficial zone cells, in which process CaSR acted as an up-streamer of PTHrP. Proteoglycan 4 specific knockout of CaSR or PTHrP reduced the cartilage thickness, suppressed the proliferation and early differentiation of the superficial zone cells, and inhibited cartilage thickening and matrix production promoted by bilateral elevation bite. Injections of CaSR agonist Cinacalcet could not improve the phenotype caused by PTHrP mutation. Injections of PTHrP87-139 peptide rescued the cartilage from knockout of CaSR gene. CaSR modulates proliferation of the superficial zone cells in mandibular condylar cartilage through activation of PTHrP nuclear localization sequence. Our data support the therapeutic target of CaSR in promoting PTHrP production in superficial zone cartilage.


Asunto(s)
Proteína Relacionada con la Hormona Paratiroidea , Receptores Sensibles al Calcio , Ratones , Animales , Proteína Relacionada con la Hormona Paratiroidea/genética , Proteína Relacionada con la Hormona Paratiroidea/metabolismo , Receptores Sensibles al Calcio/genética , Receptores Sensibles al Calcio/metabolismo , Condrocitos/metabolismo , Cartílago/metabolismo , Articulación Temporomandibular/metabolismo , Proteoglicanos/metabolismo , Proliferación Celular
11.
J Bone Miner Metab ; 2024 Jul 09.
Artículo en Inglés | MEDLINE | ID: mdl-38981876

RESUMEN

INTRODUCTION: Articular cartilage is the major affected tissue during the development of osteoarthritis (OA) in temporomandibular joint (TMJ). The core circadian rhythm molecule Bmal1 regulates chondrocyte proliferation, differentiation and apoptosis; however, its roles in condylar cartilage function and in TMJ OA have not been fully elucidated. MATERIALS AND METHODS: TMJ OA mouse model was induced by unilateral anterior crossbite (UAC) and Bmal1 protein expression in condylar cartilage were examined by western blot analysis. To determine the role of Bmal1 in TMJ OA, we generated cartilage-specific Bmal1 conditional knockout (cKO) mice (Bmal1Agc1CreER mice) and hematoxylin and eosin staining, toluidine blue and Safranin O/fast green, immunohistochemistry, TUNEL assay, real-time PCR analysis and Western blot assay were followed. RESULTS: Bmal1 expression was reduced in condylar cartilage in a TMJ OA mouse model induced by UAC. The Bmal1 cKO mice displayed decreased cartilage matrix synthesis, reduced chondrocyte proliferation, increased chondrocyte hypertrophy and apoptosis as well as the upregulation of YAP expression in TMJ condylar cartilage. CONCLUSIONS: We demonstrated that Bmal1 was essential for TMJ tissue homeostasis and loss-of-function of Bmal1 in chondrocytes leads to the development of TMJ OA.

12.
Oral Dis ; 2024 Jan 08.
Artículo en Inglés | MEDLINE | ID: mdl-38191959

RESUMEN

BACKGROUND: Temporomandibular joint disorders (TMDs) are common in young adults, and the link between chronotype profile and TMDs is unclear. OBJECTIVE: This study examined TMD prevalence and chronotype distribution and explored the relationship between chronotype and TMDs in young adults. MATERIALS AND METHODS: A total of 663 students from Sichuan University completed questionnaires. Chronotype profiles were assessed using the Morningness-Eveningness Questionnaire, and TMDs were screened using the Fonseca Memory Index. To validate the findings, 68 TMD patients and 136 controls were enrolled. RESULTS: The prevalence of TMDs was 69.7%, with significant differences among chronotype profiles. The intermediate profile was the most common chronotype. Eveningness profile was associated with higher TMDs prevalence and severity. Muscle pain and side movement difficulty scores were higher in eveningness and intermediate profiles. Female gender (OR 2.345; 95% CI 1.668-3.297) was a TMD risk factor, while morningness profile (OR 0.537; 95% CI 0.297-0.970) was protective. Validation with TMD patients and controls supported these findings, showing higher eveningness profile prevalence in the TMD groups. CONCLUSIONS: TMDs have a high prevalence in college students, chronotype profiles shown to be associated with TMDs. Morningness is the protection factor in TMDs and PT, eveningness is a risk factor for IT.

13.
Oral Dis ; 2024 May 28.
Artículo en Inglés | MEDLINE | ID: mdl-38807477

RESUMEN

OBJECTIVES: To compare masticatory muscles' recruitment in patients with temporomandibular disorders and asymptomatic control subjects. To evaluate if the masticatory muscles' recruitment pattern may predict symptoms' improvement after temporomandibular disorders treatment. MATERIALS AND METHODS: Standardized surface electromyography of anterior temporalis and superficial masseters muscles were recorded and compared at baseline in 26 patients with arthrogenous temporomandibular disorders (study group) and 26 asymptomatic subjects (control group). The study group was treated pharmacologically and by means of five arthrocentesis sessions. Pre-, during-, and post-treatment pain and mandibular function were assessed and compared among timepoints. Clinical improvement in terms of pain and mandibular function was correlated with pre-treatment standardized surface electromyography values. RESULTS: Temporomandibular disorders patients showed improved maximum mouth opening and pain during and after treatment with arthrocentesis compared to baseline (T-test p < 0.01). Standardized surface electromyography values were significantly different in temporomandibular disorders subjects compared to controls (T-test p < 0.05). Improvement in pain at rest after treatment was inversely correlated with pre-treatment masseters standardized surface electromyography symmetry (R-coefficient 0.3936; p < 0.05). CONCLUSIONS: Temporomandibular disorders patients showed a different muscular recruitment pattern compared to controls. The lesser the pre-treatment masseters symmetry, the greater the improvement of pain at rest after treatment.

14.
Oral Dis ; 2024 Jan 02.
Artículo en Inglés | MEDLINE | ID: mdl-38168877

RESUMEN

OBJECTIVES: The pathogenesis of temporomandibular joint osteoarthritis (TMJOA) remains not fully understood. Our previous studies demonstrated that miR-21-5p may participate in the TMJOA development and the interaction between circRNA-ACAP2 (CircACAP2) and miR-21-5p. Our present study aimed to explore the biological functions and regulatory mechanisms of CircACAP2 in TMJOA. MATERIALS AND METHODS: The differential expression pattern of CircACAP2 in OA and normal tissues or cells was detected. CircACAP2 biological functions experiments were performed in chondrocytes by overexpression and interference techniques. The interaction of CircACAP2 with miR-21-5p and downstream target mRNA, polymorphic adenoma gene 1 (PLAG1), was predicted by bioinformatic databases and then demonstrated by dual-luciferase reporter assay. The biological role of CircACAP2 in TMJOA was investigated and validated in a mouse model. RESULTS: The expression level of CircACAP2 was markedly reduced in OA cartilage and directly related to chondrocyte proliferation and apoptosis as well as ECM metabolism in the cartilage. CircACAP2 functioned in chondrocytes via targeting miR-21-5p and PLAG1. Overexpressing of CircACAP2 alleviated TMJOA in mouse models. CONCLUSIONS: The present study unveiled that CircACAP2/miR-21-5p/PLAG1 axis may play an important regulatory role in TMJOA progression, which may highlight a potentially effective intervention and therapeutic strategy for the treatment of TMJOA.

15.
Oral Dis ; 2024 Jan 22.
Artículo en Inglés | MEDLINE | ID: mdl-38251222

RESUMEN

OBJECTIVE: Anterior disc displacement (ADD) is a common clinical issue and may cause osteoarthritis (OA). However, the research of protein changes in synovial fluid as disease development marker and potential treatment clue is still insufficient. MATERIALS AND METHODS: We conducted the high-resolution mass spectrometry (MS) of synovial fluid collected from 60 patients with normal disk position to ADD and ADD with osteoarthritis (OA). The proteins with significant changes among the 3 groups were analyzed by biological information and further validated by in primary rat condyle chondrocytes and OA animal model. RESULTS: FGL2, THBS4, TNC, FN1, OMD etc. were significantly increased in ADD without OA (p < 0.05), which reflected the active extracellular matrix and collagen metabolism. FGFR1, FBLN2, GRB2 etc. were significantly increased in ADD with OA group (p < 0.05), which revealed an association with apoptosis and ferroptosis. Proteins such as P4HB, CBLN4, FHL1, VIM continuously increase in the whole disease progress (p < 0.05). Both the in vitro and in vivo results are consistent with protein changes detected in MS profile. CONCLUSION: This study firstly provides the expression changes of proteins from normal disc condyle relationship toward ADD with OA, which can be selected and studied further as disease progress marker and potential treatment targets.

16.
Oral Dis ; 30(2): 551-561, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36648372

RESUMEN

OBJECTIVE: The present study identified potentially pivotal miRNAs contributing to chondrogenic differentiation in temporomandibular joint suffering abnormal stress. MATERIALS AND METHODS: Sprague-Dawley rats were randomly divided into control and experimental unilateral mastication (EUM) group. Bone micro-structure parameters was detected by micro-CT, and FGF-1 and MMP-1 expression was examined by immunohistochemistry. Differentially expressed miRNAs of bilateral condyle cartilage were screened via miRNA microarray at 4- and 8-week EUM, then further verified using quantitative reverse-transcription PCR. Over-expression of five differentially expressed miRNAs in chondrocytes was triggered by transfecting miRNA mimics. The expression of MMP-13, Col-II, OPN, and Runx2 was verified by western blotting. RESULTS: Expressions of FGF-1 and MMP-1 in right condyles gradually increased from 2 to 6 weeks after EUM. A total of 20 differentially expressed miRNAs were regulated by EUM, which related to cell proliferation, invasion, and osteoblast differentiation pathways. The over-expression of miR-148a-3p and miR-1-3p led to down-regulation of Col-II, while MMP-13 and Runx2 were up-regulated by induction of hypotrophic differentiation or IL-1ß stimulation. These findings suggested that miR-148a-3p and miR-1-3p promote chondrogenic differentiation. CONCLUSIONS: Several pivotal miRNAs were found to be related to chondrogenic differentiation, which provides novel insight into pathogenic mechanisms of cartilage homeostasis.


Asunto(s)
MicroARNs , Ratas , Animales , MicroARNs/genética , Subunidad alfa 1 del Factor de Unión al Sitio Principal , Metaloproteinasa 13 de la Matriz/genética , Metaloproteinasa 1 de la Matriz , Factor 1 de Crecimiento de Fibroblastos , Masticación , Ratas Sprague-Dawley , Cartílago/metabolismo , Homeostasis
17.
Clin Rehabil ; 38(5): 623-635, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38304940

RESUMEN

OBJECTIVES: To examine the effects of acupuncture and therapeutic exercise alone and in combination on temporomandibular joint symptoms in tension-type headache and to evaluate the potential interaction of existing temporomandibular dysfunction on the success of headache treatment. DESIGN: Pre-planned secondary analysis of a randomized controlled, non-blinded trial. SETTING: Outpatient clinic of a German university hospital. SUBJECTS: Ninety-six Participants with frequent episodic or chronic tension-type headache were randomized to one of four treatment groups. INTERVENTIONS: Six weeks of acupuncture or therapeutic exercise either as monotherapies or in combination, or usual care. Follow-up at 3 and 6 months. MAIN MEASURES: Subjective temporomandibular dysfunction symptoms were measured using the Functional Questionnaire Masticatory Organ, and the influence of this sum score and objective initial dental examination on the efficacy of headache treatment interventions was analyzed. RESULTS: Temporomandibular dysfunction score improved in all intervention groups at 3-month follow-up (usual care: 0.05 [SD 1.435]; acupuncture: -5 [SD 1.436]; therapeutic exercise: -4 [SD 1.798]; combination: -3 [SD 1.504]; P = 0.03). After 6 months, only acupuncture (-6 [SD 1.736]) showed a significant improvement compared to the usual care group (P < 0.01). Subjective temporomandibular dysfunction symptoms had no overall influence on headache treatment. CONCLUSIONS: Only acupuncture had long-lasting positive effects on the symptoms of temporomandibular dysfunction. Significant dental findings seem to inhibit the efficacy of acupuncture for tension-type headache.


Asunto(s)
Terapia por Acupuntura , Trastornos de la Articulación Temporomandibular , Cefalea de Tipo Tensional , Humanos , Cefalea de Tipo Tensional/diagnóstico , Cefalea de Tipo Tensional/etiología , Cefalea de Tipo Tensional/terapia , Terapia por Ejercicio , Cefalea , Trastornos de la Articulación Temporomandibular/terapia , Resultado del Tratamiento
18.
Orthod Craniofac Res ; 27(3): 474-484, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38217321

RESUMEN

OBJECTIVE: Previous studies have shown unilateral posterior crossbite is associated with mandibular asymmetry in morphology and position. However, it remains unclear whether unilateral Brodie bite plays a similar role in mandibular development. Therefore, this study aims to investigate the morphological and positional symmetry of mandibles in patients with unilateral Brodie bite by three-dimensional anaylsis. METHODS: Fourteen patients with unilateral Brodie bite (mean age 18.43 ± 4.24 years) and fourteen sex- and age-matched patients with normal occlusion (mean age 18.07 ± 5.48 years) underwent cone-beam computed tomography (CBCT) scans. 3D surface mesh models of their mandibles were established using Mimics Research 19.0. The surface matching percentage was compared between the original and mirrored mandible by Geomagic Control X software. Furthermore, the dimension and position of the temporomandibular joint (TMJ) were determined for both groups using InVivoDental 5.0. RESULTS: For surface-to-surface deviation analysis, the percentage of mismatch in patients with unilateral Brodie bite was significantly higher than the control group at ±0.50 mm, ±0.75 mm, and ±1.00 mm tolerance (P < .001). In patients with unilateral Brodie syndrome, the condyles on the scissors-bite side showed a significantly more anterior position (P = .03), greater medial inclination (P < .01), and larger posterior TMJ space (P = .01) than the non-scissors-bite side. CONCLUSION: Patients with unilateral Brodie bite exhibit a more asymmetrical mandibular morphology, with a greater anterior condylar position and posterior joint space on the scissors-bite side, indicating that early diagnosis and treatment may be necessary for patients with unilateral Brodie bite.


Asunto(s)
Tomografía Computarizada de Haz Cónico , Asimetría Facial , Imagenología Tridimensional , Mandíbula , Articulación Temporomandibular , Humanos , Masculino , Femenino , Imagenología Tridimensional/métodos , Mandíbula/diagnóstico por imagen , Mandíbula/patología , Adolescente , Articulación Temporomandibular/diagnóstico por imagen , Articulación Temporomandibular/patología , Asimetría Facial/diagnóstico por imagen , Asimetría Facial/patología , Adulto Joven , Maloclusión/diagnóstico por imagen , Maloclusión/patología , Estudios de Casos y Controles
19.
Orthod Craniofac Res ; 27(1): 15-26, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37533308

RESUMEN

Hypoplastic asymmetry due to hemifacial microsomia (HFM) often represents the most difficult reconstruction in the craniomaxillofacial clinic. Although autogenous grafts are generally used for temporomandibular joint reconstruction (TMJR), the use of TMJR prostheses is not well established. The aim of this review was to identify, collect and analyse the use of extended TMJR (eTMJR) prostheses in patients with HFM, describing clinical features, surgical procedures and postoperative complications. Online searches of all major databases were performed according to PRISMA guidelines. All studies with HFM patients treated with the eTMJR prostheses were included. Descriptive statistics were used for data analysis. A total of 19 studies, including 08 case studies, 06 case series and 05 retrospective cohort studies, met the inclusion criteria, where a total of 42 HFM patients were reported from 18 countries, mostly from the United States (05; 26%). Fifteen of the 42 cases (~36%) were male. The mean ± SD (range) age of patients in all studies was 19.79 ± 5.81 (9-36) years. The mean ± SD (range) of patient follow-up was 41.30 ± 35.50 (6-136) months. A total of 5 (10.6%) patients were implanted with bilateral eTMJR prostheses. The Pruzansky classification was used in 18 (~89.5%) studies, OMENS classification in 01 (~5%) study, whereas no classification was reported in one study. Only 01 (7.1%) study had documented the eTMJR classification for the prosthesis used. In growing patients with or without a history of failed autogenous tissues, TMJR prostheses may provide a viable alternative. Randomized studies with large cohorts are warranted to validate these preliminary results.


Asunto(s)
Síndrome de Goldenhar , Prótesis Articulares , Trastornos de la Articulación Temporomandibular , Adolescente , Adulto , Femenino , Humanos , Masculino , Adulto Joven , Asimetría Facial , Síndrome de Goldenhar/cirugía , Síndrome de Goldenhar/complicaciones , Prótesis Articulares/estadística & datos numéricos , Estudios Retrospectivos , Articulación Temporomandibular/cirugía , Trastornos de la Articulación Temporomandibular/cirugía , Niño
20.
Orthod Craniofac Res ; 27(4): 615-625, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38456750

RESUMEN

OBJECTIVE: The objective of this prospective study was to assess possible changes in the position and shape of the temporomandibular joint (TMJ) articular disc in patients treated with two protocols of rapid maxillary expansion (RME) and face mask (FM) therapy. METHODS: A sample of 88 patients with Class III or Class III subdivision malocclusions, aged between 6 and 13 years, were consecutively selected and divided into three groups (G): G1-34 patients were treated with RME, followed by FM therapy; G2-34 patients were treated using RME according to modified alternate rapid maxillary expansion and constriction (ALT-RAMEC) protocol, followed by FM therapy. These treated groups were randomly (1:1 allocation ratio) distributed according to the two treatment protocols. G3 - Control Group - 20 untreated patients were followed. Magnetic resonance imaging (MRI) TMJs were obtained before (T1) and after (T2) a treatment period or follow-up. McNemar test, Fisher's exact test and intra- and inter-observer concordance (K) were performed (p ≤ .05). RESULTS: There were no statistically significant differences in the baseline cephalometric variables at T1 between the groups. There were statistically significant differences between the groups (p < .001) in relation to the disc shape in T1, since G1 (8 TMJs -11.76%) presented higher occurrences of altered forms in comparison with G2 (no changes). No significant differences were observed in disc position CM and OM (G1 - p > .999; G2 - p = .063; G3 - p = .500) and shape (G1 - p > 0.999; G2 - p = .250; G3 - not calculable), between T1 × T2, in any of the groups studied. CONCLUSION: The two treatment protocols did not have adverse effects on the position and shape of the TMJ disc, in a short-term evaluation.


Asunto(s)
Aparatos de Tracción Extraoral , Maloclusión de Angle Clase III , Técnica de Expansión Palatina , Disco de la Articulación Temporomandibular , Humanos , Técnica de Expansión Palatina/instrumentación , Disco de la Articulación Temporomandibular/diagnóstico por imagen , Disco de la Articulación Temporomandibular/patología , Masculino , Femenino , Adolescente , Niño , Estudios Prospectivos , Maloclusión de Angle Clase III/terapia , Imagen por Resonancia Magnética , Cefalometría , Resultado del Tratamiento , Estudios de Seguimiento
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