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1.
Gene ; 724: 144144, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31629819

RESUMO

BACKGROUND/AIMS: Rheumatoid arthritis synovial fibroblasts (RASF) play an essential role in the pathogenesis of rheumatoid arthritis (RA). This study aimed to investigate the biological effects of miR-22 on RASFs. METHODS: RT-qPCR was used to detect the expressions of miR-22 and SIRT1 in RA synovial tissue. The results of miR-22 on the proliferation of RASF were examined by MTT assay. The effects of miR-22 on the secretion of TNF-α, IL-1ß, and IL-6 in RASF were measured by ELISA. Target gene prediction and screening, and luciferase reporter assay were used to testify downstream target genes of miR-22. RT-qPCR and western blotting were used to detect the mRNA and protein expression of SIRT1. RESULTS: miR-22 was significantly decreased in RA synovial tissue, while SIRT1 was significantly increased in RA synovial tissue. Over-expression of miR-22 significantly inhibited the proliferation of RASFs and the secretions of inflammatory cytokines (TNF-α, IL-1ß, and IL-6) in RASFs. SIRT1 was identified as a direct target of miR-22. Over-expression of miR-22 reduced the expression level of SIRT1 in RASFs. Over-expression of SIRT1 reversed the effect of miR-22 on the proliferation of RASFs and the secretion of inflammatory cytokines. CONCLUSION: MIR-22 was significantly down-regulated in RASF cells, which affected the secretions of inflammatory cytokines and cell proliferation by regulating SIRT1.


Assuntos
Artrite Reumatoide/genética , Citocinas/metabolismo , MicroRNAs/genética , Sirtuína 1/genética , Membrana Sinovial/patologia , Regiões 3' não Traduzidas , Artrite Reumatoide/patologia , Proliferação de Células/genética , Citocinas/genética , Feminino , Fibroblastos/patologia , Humanos , Masculino , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Sirtuína 1/metabolismo , Membrana Sinovial/metabolismo
2.
Isr Med Assoc J ; 21(7): 454-459, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31507120

RESUMO

BACKGROUND: Platelets have the ability to influence the immune system and the inflammatory process and may be strongly involved in the whole pathogenic process of chronic inflammatory joint diseases, such as rheumatoid arthritis. They may play a significant role even before the clinical onset of the disease, contributing to the loss of tolerance of the immune system and the induction of autoimmunity. Subsequently, they can interact with the most important cellular players involved in autoimmunity and inflammation, namely innate immunity cells and T cells and eventually contribute to the building of inflammation in the synovium, thus inducing the activation, migration, and proliferation of fibroblasts that eventually lead to joint damage. Due to their peculiar features, studying the behavior of platelets is a challenging task; however, platelets may prove to be valuable therapeutic targets in the future.


Assuntos
Artrite Reumatoide/imunologia , Plaquetas/imunologia , Sinovite/imunologia , Artrite Reumatoide/patologia , Autoimunidade/imunologia , Fibroblastos/imunologia , Humanos , Imunidade Inata/imunologia , Inflamação/imunologia , Inflamação/patologia , Membrana Sinovial/imunologia , Membrana Sinovial/patologia , Sinovite/patologia , Linfócitos T/imunologia
3.
Phytomedicine ; 63: 153036, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31401534

RESUMO

BACKGROUND: Genkwanin is a flavone isolated from the traditional Chinese herb Daphne genkwa. Our previous work proved that four flavonoids (including genkwanin) isolated from D. genkwa (FFD) significantly improved the symptoms of arthritis in rat models. Recent studies have revealed that genkwanin exhibited anti-inflammatory and immunomodulatory activities, both of which were closely related to the pathology of rheumatoid arthritis (RA). Therefore, studying the anti-RA effects and mechanisms of genkwanin may give us insight into FFD's therapeutic effects on RA. PURPOSE: This study aimed to investigate the anti-rheumatoid arthritis activity of genkwanin on adjuvant-induced arthritis (AIA) model in rats and explore the underlying mechanisms. METHODS: The anti-rheumatoid arthritis activity of genkwanin was evaluated on AIA rat model by determining the paw swelling degrees and arthritis index scores, along with histopathological analysis of joint tissues. The serum cytokine levels were measured by ELISA method, and serum NO levels were measured by Griess method. The expression and phosphorylation levels of proteins in JAK/STAT and NF-κB signaling pathways were determined by western blot analysis and immunohistochemistry analysis. RESULTS: Genkwanin significantly decreased the paw swelling and arthritis index in AIA rats and also decreased the inflammation and bone destruction in joint tissues. The serum TNF-α, IL-6, and NO concentrations were markedly reduced while the IL-10 concentration was markedly increased with the treatment of genkwanin. Genkwanin inhibited the activation of JAK/STAT and NF-κB signaling pathways in synovial tissues of AIA rats. CONCLUSION: Genkwanin exerted anti-rheumatoid arthritis effects on AIA rats through inhibiting the activation of JAK/STAT and NF-κB signaling pathways. The results obtained in this work lead us to suggest that Genkwanin could play a crucial role on the previously demonstrated anti-rheumatoid arthritis activity of flavonoid extract of D. genkwa (namely FFD).


Assuntos
Artrite Experimental/tratamento farmacológico , Artrite Reumatoide/tratamento farmacológico , Flavonas/farmacologia , NF-kappa B/metabolismo , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Artrite Experimental/metabolismo , Artrite Reumatoide/metabolismo , Citocinas/sangue , Citocinas/metabolismo , Inflamação/tratamento farmacológico , Inibidores de Janus Quinases/farmacologia , Masculino , Fosforilação/efeitos dos fármacos , Ratos Sprague-Dawley , Fatores de Transcrição STAT/antagonistas & inibidores , Fatores de Transcrição STAT/metabolismo , Transdução de Sinais/efeitos dos fármacos , Membrana Sinovial/efeitos dos fármacos , Membrana Sinovial/metabolismo , Membrana Sinovial/patologia
4.
Inflamm Res ; 68(10): 889-900, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31372663

RESUMO

OBJECTIVE: To investigate the participation of canonical Wnt and NF-κB signaling pathways in an experimental model of chronic arthritis induced by methylated bovine serum albumin (mBSA) in rat temporomandibular joint (TMJ). MATERIALS AND METHODS: Wistar rats were sensitized by mBSA+Complete Freund Adjuvant (CFA)/Incomplete Freund Adjuvant (IFA) on the first 14 days (1 ×/week). Subsequently, they received 1, 2 or 3 mBSA or saline solution injections into the TMJ (1 ×/week). Hypernociceptive threshold was assessed during the whole experimental period. 24 h after the mBSA injections, the TMJs were removed for histopathological and immunohistochemical analyses for TNF-α, IL-1ß, NF-κB, RANKL, Wnt-10b, ß-catenin and DKK1. RESULTS: The nociceptive threshold was significantly reduced after mBSA injections. An inflammatory infiltrate and thickening of the synovial membrane were observed only after mBSA booster injections. Immunolabeling of TNF-α, IL-1ß and Wnt-10b was increased in the synovial membrane in arthritic groups. The immunoexpression of nuclear ß-catenin was significantly higher only in the group that received 2 booster TMJ injections. However, NF-κB, RANKL and DKK1 immunoexpression were increased only in animals with 3 mBSA intra-articular injections. CONCLUSION: Our results suggest that canonical Wnt and NF-κB signaling pathways participate in the hypernociception and inflammatory response in TMJ synovial membrane during the development of rheumatoid arthritis in rats.


Assuntos
Artrite Experimental/imunologia , Artrite Reumatoide/imunologia , Hiperalgesia/imunologia , NF-kappa B/imunologia , Articulação Temporomandibular/imunologia , Via de Sinalização Wnt , Animais , Artrite Experimental/patologia , Artrite Reumatoide/patologia , Adjuvante de Freund , Hiperalgesia/patologia , Peptídeos e Proteínas de Sinalização Intercelular/imunologia , Interleucina-1beta/imunologia , Lipídeos , Masculino , Ligante RANK/imunologia , Ratos Wistar , Soroalbumina Bovina , Membrana Sinovial/imunologia , Membrana Sinovial/patologia , Articulação Temporomandibular/patologia , Fator de Necrose Tumoral alfa/imunologia , Proteínas Wnt/imunologia
5.
Int J Mol Sci ; 20(13)2019 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-31288389

RESUMO

Nanobody against V-set and Ig domain-containing 4 (Vsig4) on tissue macrophages, such as synovial macrophages, could visualize joint inflammation in multiple experimental arthritis models via single-photon emission computed tomography imaging. Here, we further addressed the specificity and assessed the potential for arthritis monitoring using near-infrared fluorescence (NIRF) Cy7-labeled Vsig4 nanobody (Cy7-Nb119). In vivo NIRF-imaging of collagen-induced arthritis (CIA) was performed using Cy7-Nb119. Signals obtained with Cy7-Nb119 or isotope control Cy7-NbBCII10 were compared in joints of naive mice versus CIA mice. In addition, pathological microscopy and fluorescence microscopy were used to validate the arthritis development in CIA. Cy7-Nb119 accumulated in inflamed joints of CIA mice, but not the naive mice. Development of symptoms in CIA was reflected in increased joint accumulation of Cy7-Nb119, which correlated with the conventional measurements of disease. Vsig4 is co-expressed with F4/80, indicating targeting of the increasing number of synovial macrophages associated with the severity of inflammation by the Vsig4 nanobody. NIRF imaging with Cy7-Nb119 allows specific assessment of inflammation in experimental arthritis and provides complementary information to clinical scoring for quantitative, non-invasive and economical monitoring of the pathological process. Nanobody labelled with fluorescence can also be used for ex vivo validation experiments using flow cytometry and fluorescence microscopy.


Assuntos
Artrite Experimental/diagnóstico , Artrite Experimental/metabolismo , Macrófagos/metabolismo , Imagem Molecular/métodos , Receptores de Complemento , Anticorpos de Domínio Único , Membrana Sinovial/metabolismo , Membrana Sinovial/patologia , Animais , Imunofluorescência , Corantes Fluorescentes/química , Imuno-Histoquímica , Macrófagos/imunologia , Masculino , Camundongos , Microscopia de Fluorescência , Modelos Moleculares , Estrutura Molecular , Receptores de Complemento/imunologia , Anticorpos de Domínio Único/química , Anticorpos de Domínio Único/imunologia , Espectroscopia de Luz Próxima ao Infravermelho , Coloração e Rotulagem , Membrana Sinovial/imunologia
6.
Eklem Hastalik Cerrahisi ; 30(2): 177-81, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31291869

RESUMO

Pigmented villonodular synovitis (PVNS) is a benign tumorous condition commonly found in tendon sheathes, bursa, or joint synovium. Unlike the diffuse type which invades the entire synovium of the affected joint, synovium of localized PVNS shows relatively normal appearance. It presents nonspecific symptoms and typically progresses for a long time but acute locking phenomenon or internal derangement of knee symptoms suddenly commence in early stage. In this article, we present a 48-year-old female patient with well-capsulated localized PVNS with intra-capsular hemorrhage occurring from the junction of the mid-body of lateral meniscus and the lateral joint capsule in the knee. It expanded and then moved to the lateral joint space, which caused pain, limitation of knee flexion and locking spontaneously. Arthroscopic complete excision, biopsy, and focal synovectomy were performed with punch and motorized shaver. Full weight-bearing with full knee range of motion was allowed at one day post-surgery. The mechanical symptom of locking and severe pain disappeared. At the clinical follow-up one month post-surgery, the symptoms were no longer present.


Assuntos
Doenças das Cartilagens/etiologia , Hemorragia/etiologia , Sinovite Pigmentada Vilonodular/complicações , Sinovite Pigmentada Vilonodular/cirurgia , Artroscopia , Biópsia , Feminino , Humanos , Cápsula Articular , Articulação do Joelho/cirurgia , Meniscos Tibiais/cirurgia , Pessoa de Meia-Idade , Sinovectomia , Membrana Sinovial/patologia , Sinovite Pigmentada Vilonodular/diagnóstico por imagem , Sinovite Pigmentada Vilonodular/patologia
7.
Scand J Rheumatol ; 48(5): 383-392, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31354003

RESUMO

Objectives: The discovery of alternative and well-tolerated anti-arthritic drugs, especially from natural products, is becoming an area of active research. Pedunculoside (PE) is a novel triterpene saponin extracted from the dried bark of Ilex rotunda Thunb. Limited published papers have reported its pharmacological properties, including anti-inflammatory, anti-myocardial ischaemia, anti-liver injury, and hypocholesterolaemic activities. However, the effect of PE on rheumatoid arthritis (RA) remains unknown. Here, we investigated the anti-arthritic effect of PE in both in vitro and in vivo models. Method: The inhibitory effects of PE on proliferation, migration, and production of inflammatory mediators in primary fibroblast-like synoviocytes (FLSs) were examined by a 5-ethynyl-2'-deoxyuridine incorporation assay, wound-healing assay, and real-time polymerase chain reaction, respectively. Cellular signalling mechanisms were analysed by Western blot. The in vivo studies were performed using a collagen-induced arthritis (CIA) rat model. Multiple methods, including arthritis scoring, enzyme-linked immunoassay, radiography, and histopathological assessment, were used to evaluate the therapeutic effects of PE on CIA rats. Results: The in vitro studies revealed that PE significantly inhibited proliferation and migration of FLSs. PE also decreased the production of pro-inflammatory cytokines, including interleukin-1ß (IL-1ß), IL-6, IL-8, and tumour necrosis factor-α (TNF-α). Western blot results suggested that PE suppressed TNF-α-stimulated activation of p38 and extracellular signal-regulated kinase. The in vivo studies showed that PE treatment significantly inhibited synovial inflammation and bone destruction in CIA rats. Conclusion: These results demonstrate that PE exerts an inhibitory role in FLSs and CIA rats, and therefore may have therapeutic value for the treatment of RA.


Assuntos
Artrite Experimental/tratamento farmacológico , Desoxicitidina/análogos & derivados , Glucose/análogos & derivados , Membrana Sinovial/patologia , Triterpenos/farmacologia , Animais , Artrite Experimental/diagnóstico , Artrite Experimental/metabolismo , Proliferação de Células , Células Cultivadas , Citocinas/metabolismo , Desoxicitidina/metabolismo , Medicamentos de Ervas Chinesas , Feminino , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Fibroblastos/patologia , Citometria de Fluxo , Glucose/farmacologia , Fenótipo , Radiografia , Ratos , Ratos Wistar , Membrana Sinovial/metabolismo
8.
Int Immunopharmacol ; 73: 539-551, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31177080

RESUMO

OBJECTIVE: We aimed to investigate the immunologic mechanisms by which arsenic trioxide (As2O3) may inhibit T helper 17 (Th17) cell differentiation while promoting regulatory T (Treg) cell generation by modulating signal transducer and activator of transcription 3 (STAT3) in treatment-naïve rheumatoid arthritis (RA) patients. METHODS: Naïve CD4+T cells isolated by fluorescence-activated cell sorting from treatment-naïve RA patients and healthy controls were used to investigate the effect of As2O3 on the process of polarization and the related cytokines. STAT3 transfection experiments were conducted with small interfering RNA (siRNA) and lentivirus STAT3 to verify the mechanism of As2O3 on Th17-Treg balance in vitro. A collagen-induced arthritis (CIA) model was used to detect the clinical scores, histopathological change, bone destruction, Th17-Treg proportion and joint tissue immunohistochemistry. RESULTS: We found that As2O3 prevented activated naïve CD4+T-cells from differentiating into Th17 cells and reduced cytokine production by activated Th17 cells by downregulating their signature transcription factors, STAT3 and orphan nuclear receptors. Notably, As2O3 reduced Th17 cells frequency while increasing Treg cells frequency under specific polarizing conditions in treatment-naïve RA patients by transfecting siRNA STAT3 and lentivirus STAT3. Furthermore, we noticed that applying As2O3 in the CIA model attenuated the infiltration of joint inflammation and bone destruction, and significantly improved the imbalanced Treg-Th17 ratio. CONCLUSIONS: These data indicate that As2O3 may be a potential immune modulator for treatment-naïve RA patients that helps to balance of Treg and Th17 cells through modulating STAT3.


Assuntos
Trióxido de Arsênio/farmacologia , Artrite Reumatoide/imunologia , Fatores Imunológicos/farmacologia , Fator de Transcrição STAT3/imunologia , Linfócitos T Reguladores/efeitos dos fármacos , Células Th17/efeitos dos fármacos , Adulto , Animais , Trióxido de Arsênio/uso terapêutico , Artrite Experimental/tratamento farmacológico , Artrite Experimental/imunologia , Artrite Experimental/patologia , Citocinas/imunologia , Feminino , Humanos , Fatores Imunológicos/uso terapêutico , Articulações/efeitos dos fármacos , Articulações/patologia , Masculino , Camundongos Endogâmicos DBA , Pessoa de Meia-Idade , Baço/efeitos dos fármacos , Baço/imunologia , Membrana Sinovial/efeitos dos fármacos , Membrana Sinovial/imunologia , Membrana Sinovial/patologia , Linfócitos T Reguladores/imunologia , Células Th17/imunologia
9.
BMC Musculoskelet Disord ; 20(1): 286, 2019 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-31200688

RESUMO

BACKGROUND: McH-lpr/lpr-RA1 mice are a new strain of mice which spontaneously develop destructive arthritis and enthesitis in the ankle. There is no published data that drug treatment has been trialed on these mice. This study examined the effect of the mouse anti-IL-6 receptor antibody, MR16-1, for the treatment of arthritis and enthesitis in McH-lpr/lpr-RA1 mice. METHODS: Male McH-lpr/lpr-RA1 mice were randomly divided into control and treatment groups. MR16-1 was administered from 10 weeks of age for the treatment group. Saline was applied for the control group. The drug was administered once a week, at an initial dose of 2 mg, then maintained at 0.5 mg once per week thereafter. The effects were evaluated by the histopathological synovitis score, in vivo imaging using indocyanine green liposomes, and analysis of the gene expression of inflammatory cytokines. RESULTS: Tissue analyses were carried out at 14, 17 and 20 weeks of age. The synovitis scores of treated groups were significantly lower compared with those of the control group at 14 and 17 weeks of age. The kappa coefficient was 0.77. However, progression of entheseal ossification persisted in the MR16-1 treated group. In vivo imaging using indocyanine green liposomes showed significant decreases in signal intensities of treated groups at week 14, but no significant differences were observed at week 18. Blood serum amyloid A levels in treated groups were significantly lower at 17 weeks of age. The gene expression levels of Tnf and Il17 were also significantly lower in MR16-1 treated groups. CONCLUSIONS: Administration of the anti-IL-6 receptor antibody is effective for the treatment of synovitis and bone destruction of McH-lpr/lpr-RA1 mice. McH-lpr/lpr-RA1 mice may be a suitable experimental model for the development of new treatments for destructive arthritis and enthesitis. IL-6 signal blockade could contribute to the treatment of destructive arthritis, and further studies should be carried out to confirm its potential in the prevention of enthesopathy developed to ossification.


Assuntos
Anticorpos/administração & dosagem , Artrite/tratamento farmacológico , Entesopatia/tratamento farmacológico , Receptores de Interleucina-6/antagonistas & inibidores , Animais , Artrite/imunologia , Artrite/patologia , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Entesopatia/imunologia , Entesopatia/patologia , Humanos , Injeções Intraperitoneais , Masculino , Camundongos , Camundongos Endogâmicos , Distribuição Aleatória , Receptores de Interleucina-6/imunologia , Membrana Sinovial/efeitos dos fármacos , Membrana Sinovial/imunologia , Membrana Sinovial/patologia
10.
APMIS ; 127(8): 588-593, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31233243

RESUMO

Microfibrillar-associated protein 4 (MFAP4) is a non-structural matrix protein with cell regulatory activities and a potential as seromarker for fibrosis. We aimed to study the occurrence of MFAP4 in the synovial membrane from patients with rheumatoid arthritis (RA) vs osteoarthritis (OA). Formaldehyde-fixed synovial tissue sections, from patients with RA (N = 6) and OA (N = 6) undergoing total hip arthroplasty, were deparaffinized and immunostained with monoclonal antibodies against MFAP4. Elastin was detected using ElastiKit. MFAP4 in serum (sMFAP4) and synovial fluid was measured by an immunoassay. MFAP4 was present in synovial biopsies from both RA and OA patients, particularly prominent in deep arterioles where it colocalized with elastin. Notably however, MFAP4 was absent from the internal elastic lamina in RA arterioles irrespective of disease duration and synovitis activity, while present although with irregular staining patterns in OA specimens. sMFAP4 was increased in RA and OA serum vs healthy controls: median (interquartile range) 29.8 (25.3-39.1) and 25.5 U/L (18.1-43.3) vs 17.7 U/L (13.7-21.2), p = 0.006 and p = 0.02, respectively The concentration of synovial fluid was lower than in serum in both RA and OA. These findings may suggest that MFAP4 is involved in adaptive vessel wall remodeling associated with chronic joint disease.


Assuntos
Artrite Reumatoide/imunologia , Proteínas de Transporte/análise , Proteínas da Matriz Extracelular/análise , Glicoproteínas/análise , Osteoartrite/imunologia , Membrana Sinovial/imunologia , Idoso , Anticorpos Monoclonais/imunologia , Biomarcadores/análise , Proteínas de Transporte/imunologia , Estudos de Casos e Controles , Proteínas da Matriz Extracelular/imunologia , Feminino , Glicoproteínas/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Líquido Sinovial/química , Membrana Sinovial/patologia
11.
Nat Immunol ; 20(7): 928-942, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31061532

RESUMO

To define the cell populations that drive joint inflammation in rheumatoid arthritis (RA), we applied single-cell RNA sequencing (scRNA-seq), mass cytometry, bulk RNA sequencing (RNA-seq) and flow cytometry to T cells, B cells, monocytes, and fibroblasts from 51 samples of synovial tissue from patients with RA or osteoarthritis (OA). Utilizing an integrated strategy based on canonical correlation analysis of 5,265 scRNA-seq profiles, we identified 18 unique cell populations. Combining mass cytometry and transcriptomics revealed cell states expanded in RA synovia: THY1(CD90)+HLA-DRAhi sublining fibroblasts, IL1B+ pro-inflammatory monocytes, ITGAX+TBX21+ autoimmune-associated B cells and PDCD1+ peripheral helper T (TPH) cells and follicular helper T (TFH) cells. We defined distinct subsets of CD8+ T cells characterized by GZMK+, GZMB+, and GNLY+ phenotypes. We mapped inflammatory mediators to their source cell populations; for example, we attributed IL6 expression to THY1+HLA-DRAhi fibroblasts and IL1B production to pro-inflammatory monocytes. These populations are potentially key mediators of RA pathogenesis.


Assuntos
Artrite Reumatoide/genética , Artrite Reumatoide/metabolismo , Perfilação da Expressão Gênica , Membrana Sinovial/metabolismo , Transcriptoma , Artrite Reumatoide/patologia , Autoimunidade/genética , Biomarcadores , Biologia Computacional/métodos , Estudos Transversais , Citocinas/metabolismo , Fibroblastos/metabolismo , Citometria de Fluxo , Expressão Gênica , Perfilação da Expressão Gênica/métodos , Sequenciamento de Nucleotídeos em Larga Escala , Antígenos de Histocompatibilidade Classe II/genética , Antígenos de Histocompatibilidade Classe II/imunologia , Humanos , Leucócitos/imunologia , Leucócitos/metabolismo , Monócitos/imunologia , Monócitos/metabolismo , Transdução de Sinais , Análise de Célula Única/métodos , Membrana Sinovial/patologia , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo , Fluxo de Trabalho
12.
Biomed Res Int ; 2019: 6390182, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31049352

RESUMO

Osteoarthritis (OA) is the most common form of joint disease and a major cause of pain and disability in the adult population. Interestingly, there are patients with symptomatic OA displaying pain, while patients with asymptomatic OA that do not experience pain but show radiographic signs of joint damage. Pain is a complex experience integrating sensory, affective, and cognitive processes related to several peripheral and central nociceptive factors besides inflammation. During the last years, the role of infrapatellar fat pad (IFP), other than the synovial membrane, has been investigated as a potential source of pain in OA. Interestingly, new findings suggest that IFP and synovial membrane might act as a functional unit in OA pathogenesis and pain. The present review discuss the role of IFP and synovial membrane in the development of OA, with a particular focus on pain onset and the possible involved mediators that may play a role in OA pathology and pain mechanisms. Inflammation of IFP and synovial membrane may drive peripheral and central sensitization in KOA. Since sensitization is associated with pain severity in knee OA and may potentially contribute to the transition from acute to chronic, persistent pain in knee OA, preventing sensitization would be a potentially effective and novel means of preventing worsening of pain in knee OA.


Assuntos
Tecido Adiposo/patologia , Osteoartrite do Joelho/patologia , Patela/patologia , Animais , Humanos , Inflamação/patologia , Articulação do Joelho/patologia , Dor/patologia , Membrana Sinovial/patologia
13.
Medicine (Baltimore) ; 98(18): e15497, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31045835

RESUMO

Synovial plica is rarely diagnosed as cause of elbow pain. Impingemnt of posterolateral plicae in the radiocapitellar joint tends to be usually overlooked. The purpose of this study was to present outcomes of arthroscopic treatment in relatively large number of cases and propose reliable diagnostic test for posterolateral plicae of the radiocapitellar joint.From January 2000 to December 2010, 24 cases diagnosed with pathologic posterolateral radiocapitellar plica on arthroscopic finding were retrospectively reviewed. Magnetic resonance imaging (MRI) evaluation and preoperative physical examination were performed. The posterolateral radiocapitellar plica test newly proposed by the present study was also conducted. To measure postoperative clinical outcomes, the disabilities of the arm, shoulder, and hand (DASH) score and Mayo elbow performance score (MEPS) were employed. Minimum duration of follow up was 24 months.According to the preoperative MRI, pathologic radiocapitellar plica was identified in 17 cases (70.8%). Preoperatively, maximal tender point was present on the radiocapitellar joint line in 20 cases (83.3%) and mechanical symptoms were observed in 9 cases (37.5%). 6 cases (25%) demonstrated pain at terminal extension and limitation of extension. 20 (83.3%) cases tested positive for posterolateral radiocapitellar plica test. The sensitivity and specificity of the posterolateral radiocapitellar plica test were 83.3% and 87.5%, respectively. The accuracy value was 86.3%. Arthroscopic debridement of pathologic plica in the radiocapitellar joint demonstrated clinical improvements: DASH score was from 36.6 to 8.9 and MEPS was from 56.9 to 95.6 at the latest follow-up.Symptomatic impingement by the pathologic posterolateral plica of the radiocapitellar joint should be considered when posterolateral elbow pain which is refractory to conservative treatment, and other prevalent diseases are excluded. The posterolateral radiocapitellar plica test and radiocapitellar joint line tenderness could be recommended as reliable examination maneuvers to obtain accurate diagnosis. Arthroscopic debridement was an effective method for treating symptomatic plicae.


Assuntos
Artroscopia/métodos , Desbridamento/métodos , Artropatias/diagnóstico , Artropatias/cirurgia , Adolescente , Adulto , Artralgia/etiologia , Articulação do Cotovelo/diagnóstico por imagem , Articulação do Cotovelo/patologia , Articulação do Cotovelo/cirurgia , Feminino , Humanos , Artropatias/complicações , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Membrana Sinovial/diagnóstico por imagem , Membrana Sinovial/patologia , Adulto Jovem
14.
BMC Musculoskelet Disord ; 20(1): 204, 2019 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-31077183

RESUMO

BACKGROUND: Nerve growth factor (NGF) contributes to pain in knee osteoarthritis (KOA) patients. Transforming growth factor-beta (TGF-ß) stimulates NGF expression in chondrocytes from KOA patients. However, the correlation between synovial TGF-ß and NGF levels has not been sufficiently studied in human KOA patients. Further, the mechanism governing NGF regulation by TGF-ß in synovial cells is unclear. METHODS: During total knee arthroplasty, we extracted the synovial tissue (SYT) of 107 subjects with unilateral Kellgren/Lawrence grade 3-4 KOA confirmed by radiography. We examined the distribution of TGF-ß and NGF using immunohistochemistry, and analyzed the relationship between NGF and TGFB mRNA levels. Cultured synovial cells extracted from SYT were exposed to culture medium (control), human recombinant TGF-ß (rhTGF-ß), rhTGF-ß + ALK5 inhibitor SB505124, rhTGF-ß + transforming growth factor activating kinase 1 (TAK1) inhibitor (5Z)-7-oxozeaenol, or rhTGF-ß + p38 inhibitor SB203580 for 30 min, 6 h and 24 h. NGF mRNA expressed by the cultured cells and NGF protein levels in the cell supernatant were detected by real-time polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA), respectively. Phosphorylation of p38 was evaluated by western blotting. RESULTS: NGF mRNA levels were positively correlated with those of TGFB. Cells expressing TGF-ß and NGF protein were observed in the lining layer of SYT. TGF-ß stimulated increased NGF mRNA expression and NGF protein production. The ALK5 inhibitor completely suppressed the TGF-ß-mediated increase in NGF expression and NGF production in synovial cells. ALK5, TAK1 and p38 inhibitors inhibited the TGF-ß-induced phosphorylation of p38, and TAK1 and p38 inhibitors partially inhibited the TGF-ß-mediated increase in NGF expression and NGF production in synovial cells. CONCLUSION: TGF-ß regulates NGF production via the TGF-ß/ALK5 signaling pathway in osteoarthritic synovium. This effect may partially occur through inhibition of the TAK1/p38 pathway in the SYT of KOA patients.


Assuntos
Artralgia/patologia , Fator de Crescimento Neural/metabolismo , Osteoartrite do Joelho/complicações , Membrana Sinovial/patologia , Fator de Crescimento Transformador beta1/metabolismo , Idoso , Artralgia/etiologia , Células Cultivadas , Feminino , Humanos , Masculino , Osteoartrite do Joelho/patologia , Cultura Primária de Células , Membrana Sinovial/citologia , Sinoviócitos/metabolismo
15.
Tohoku J Exp Med ; 248(1): 13-17, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31080194

RESUMO

Synovial fat deposition, also known as lipoma arborescens, is a rare articular disorder with villous synovial proliferation, commonly seen in the knee. We explored the relationship between the degree of synovial fat deposition on the magnetic resonance imaging (MRI) and the severity of degenerative joint disorder, also called osteoarthritis, on plain radiography. The enrolled patients underwent MRI with a 0.4T permanent magnetic unit in a single institution over a 9-month period. The indications of MRI were chronic knee disorder of non-specific cause. Patients with minor trauma were also included. Consecutive 1,091 knees of 1,075 patients were assessed for the degree of synovial fat deposition on MRI and the severity of degenerative joint disorder on plain radiography. The degenerative joint disorder was graded by radiographic features obtained within one month from MRI using Kellgrene-Lawrence (K-L) scores. MRI features of synovial fat deposition were classified as none, mild and severe. Synovial fat deposition was identified in 30 knees of 29 patients (2.7%) (11 men and 18 women; aged from 25 to 86 years, one patient with bilateral lesions): one female patient with osteoarthritis secondary to rheumatoid arthritis and 28 patients with degenerative joint disorder. The K-L grade was 4 in the case of rheumatoid arthritis. There was a moderate positive correlation between the K-L grade and fat deposition grade (correlation coefficient: 0.59, p < 0.001). Thus, synovial fat deposition was noted in the advanced degenerative joint disorder. We propose that fat deposition represents a nonspecific secondary phenomenon of degenerative joint disorder.


Assuntos
Adiposidade , Artropatias/patologia , Articulação do Joelho/patologia , Membrana Sinovial/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Artrite Reumatoide/diagnóstico por imagem , Artrite Reumatoide/patologia , Feminino , Humanos , Artropatias/diagnóstico por imagem , Articulação do Joelho/diagnóstico por imagem , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Membrana Sinovial/diagnóstico por imagem , Adulto Jovem
16.
Int Immunopharmacol ; 73: 362-369, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31132731

RESUMO

Apigenin (API) is a plant flavone that is known to exert a protective effect in rheumatoid arthritis (RA), which is a chronic autoimmune disease. However, the molecular mechanism for API's protective effect against RA is still unclear. Here, a collagen-induced arthritis (CIA) mouse model was used to assess the protective effect of API on RA. Histomorphological studies, immunohistochemistry, RT-PCR, and western blot were conducted to elucidate the roles of synovial hyperplasia, angiogenesis, and osteoclastogenesis in the protective effect of API on RA. Fibroblast-like synoviocytes (FLSs) were isolated to measure the effect of API on FLS proliferation and apoptosis. API exhibited a significant protective effect in CIA mice in a dose- and time-dependent manner. An increase in apoptosis and decrease in proliferation were observed after the API treatment in FLSs, suggesting that API might inhibit synovial hyperplasia. Moreover, CIA angiogenesis was repressed by API via down-regulation of VEGF and VEGFR. Furthermore, API regulated the osteoclastogenesis-associated RANKL/RANK/OPG system in CIA mice. Therefore, API inhibits CIA by repressing synovial hyperplasia, angiogenesis, and osteoclastogenesis. This suggested that API might be a putative low toxicity candidate drug for RA treatment.


Assuntos
Antirreumáticos/uso terapêutico , Apigenina/uso terapêutico , Artrite Experimental/tratamento farmacológico , Artrite Reumatoide/tratamento farmacológico , Animais , Antirreumáticos/farmacologia , Apigenina/farmacologia , Apoptose/efeitos dos fármacos , Artrite Experimental/genética , Artrite Experimental/metabolismo , Artrite Experimental/patologia , Artrite Reumatoide/genética , Artrite Reumatoide/metabolismo , Artrite Reumatoide/patologia , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Hiperplasia/tratamento farmacológico , Hiperplasia/genética , Hiperplasia/metabolismo , Hiperplasia/patologia , Masculino , Camundongos Endogâmicos DBA , Neovascularização Fisiológica/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Ligante RANK/metabolismo , Receptor Ativador de Fator Nuclear kappa-B/metabolismo , Receptores de Fatores de Crescimento do Endotélio Vascular/genética , Receptores de Fatores de Crescimento do Endotélio Vascular/metabolismo , Membrana Sinovial/efeitos dos fármacos , Membrana Sinovial/patologia , Sinoviócitos/efeitos dos fármacos , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo
17.
Cell Mol Biol Lett ; 24: 8, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31019537

RESUMO

Background: This study aimed to investigate the effects of miR-613 on the proliferation, invasion and apoptosis of rheumatoid arthritis synovial fibroblasts (RASFs). Methods: Synovial tissue samples were collected from 20 rheumatoid arthritis (RA) patients and 10 patients with joint trauma undergoing joint replacement surgery. The RASFs were isolated and cultured. MiR-613 and DKK1 expression in both synovial tissues and cells was detected using quantitative real-time PCR (qRT-PCR). Dual luciferase reporter gene assay was employed to evaluate the effect of miR-613 on the luciferase activity of DKK1. Then RASFs were transfected with miR-613 mimics, si-DKK1 and pcDNA-DKK1. Changes in cellular proliferation, invasion and apoptosis were detected through BrdU assay, Transwell invasion assay and flow cytometry analysis, respectively. Results: MiR-613 was significantly down-regulated in RA tissues and RASFs compared to normal tissues and cells, whereas DKK1 was up-regulated in RA tissues and RASFs. Dual luciferase reporter gene assay showed that miR-613 could specifically bind to the 3'UTR of DKK1 and significantly inhibit the luciferase activity. Moreover, miR-613 significantly reduced the expression of DKK1. Overexpression of miR-613 or knockdown of DKK1 suppressed proliferation and invasion of RASFs, and induced RASF apoptosis. The reverse results were observed when DKK1 was up-regulated in miR-613-overexpressing RASFs. Conclusions: MiR-613 can inhibit proliferation and invasion and induce apoptosis of RASFs by directly targeting DKK1 expression.


Assuntos
Apoptose , Artrite Reumatoide/patologia , Movimento Celular , Regulação para Baixo/genética , Fibroblastos/patologia , Peptídeos e Proteínas de Sinalização Intercelular/genética , MicroRNAs/metabolismo , Membrana Sinovial/patologia , Regiões 3' não Traduzidas/genética , Adulto , Idoso , Apoptose/genética , Artrite Reumatoide/genética , Sequência de Bases , Ciclo Celular/genética , Movimento Celular/genética , Proliferação de Células/genética , Feminino , Técnicas de Silenciamento de Genes , Inativação Gênica , Humanos , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , Regulação para Cima/genética
18.
Int J Mol Sci ; 20(8)2019 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-31027208

RESUMO

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease characterized by inflammation of the synovial membrane, with thickening of the synovial layer, cellular hyperplasia, and infiltration of immune cells. Mast cells (MCs) are cells of the innate immunity present in healthy synovia and part of the cellular hyperplasia characterizing RA synovitis. Although their presence in synovia has been well described, the exact functions and the correlation of MCs with disease development and progression have been debated, particularly because of contradictory data obtained in animal models and from patients with longstanding disease. Here, we present a revision of the literature on MCs in RA, including the most recent observations obtained from patients with early RA, indicating MCs as relevant markers of disease severity in early RA.


Assuntos
Artrite Reumatoide/patologia , Mastócitos/patologia , Animais , Artrite Reumatoide/imunologia , Humanos , Imunomodulação , Inflamação/patologia , Ativação Linfocitária/imunologia , Membrana Sinovial/imunologia , Membrana Sinovial/patologia
19.
Eur J Orthop Surg Traumatol ; 29(6): 1291-1296, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30980138

RESUMO

BACKGROUND: Synovial hemangioma is a benign intra-articular tumor. This condition is rare and unfamiliar soft tissue tumor to most orthopedic surgeons. Delayed diagnosis causes osteoarthritic damage and the destruction of joint structures due to infiltrating tumor growth. We discuss the patterns of tumor location and the appropriate surgical procedure for this condition. METHODS: Ten patients were treated surgically in our department. These comprised five males and five females ranging in age from 0 to 17 years (average age 12.4 years). Preoperative diagnosis was made using clinical findings, plain radiographs and magnetic resonance imaging. The follow-up time after surgery was at least 3 years. RESULTS: The main symptom was pain. Three cases revealed hemarthrosis. The range of motion of the affected knee joint was limited in five cases. The average time between onset of pain and diagnosis was 3 years. Tumor location was classified into three patterns: (1) anterior patellofemoral joint type in five, (2) posterior popliteal type in two and (3) diffuse proliferation type in two. Open arthrotomy with synovectomy was performed in all cases. No tumor recurrences were experienced after a minimum follow-up of 3 years. CONCLUSION: Clinical symptom and magnetic resonance imaging are helpful to obtain the diagnosis and determine the extent of the lesion. Depending on the tumor location, synovial hemangioma in the knee joint can be classified into patellofemoral, popliteal and diffuse types. Open arthrotomy with sufficient tumor and synovectomy is important to prevent tumor recurrence.


Assuntos
Diagnóstico Tardio/prevenção & controle , Hemangioma , Artropatias , Articulação do Joelho , Neoplasias de Tecidos Moles , Sinovectomia/métodos , Membrana Sinovial , Artralgia/diagnóstico , Artralgia/etiologia , Criança , Diagnóstico Tardio/efeitos adversos , Feminino , Hemangioma/patologia , Hemangioma/fisiopatologia , Hemangioma/cirurgia , Humanos , Artropatias/patologia , Artropatias/fisiopatologia , Artropatias/cirurgia , Articulação do Joelho/diagnóstico por imagem , Articulação do Joelho/fisiopatologia , Articulação do Joelho/cirurgia , Imagem por Ressonância Magnética/métodos , Masculino , Radiografia/métodos , Amplitude de Movimento Articular , Neoplasias de Tecidos Moles/patologia , Neoplasias de Tecidos Moles/fisiopatologia , Neoplasias de Tecidos Moles/cirurgia , Membrana Sinovial/diagnóstico por imagem , Membrana Sinovial/patologia , Resultado do Tratamento
20.
PLoS One ; 14(3): e0212662, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30822327

RESUMO

Surgical transection of the anterior cruciate ligament (ACL) in the porcine model leads to posttraumatic osteoarthritis if left untreated. However, a recently developed surgical treatment, bridge-enhanced ACL repair, prevents further cartilage damage. Since the synovial fluid bathes all the intrinsic structures of knee, we reasoned that a comparative analysis of synovial fluid protein contents could help to better understand the observed chondroprotective effects of the bridge-enhanced ACL repair. We hypothesized that post-surgical changes in the synovial fluid proteome would be different in the untreated and repaired knees, and those changes would correlate with the degree of cartilage damage. Thirty adolescent Yucatan mini-pigs underwent unilateral ACL transection and were randomly assigned to either no further treatment (ACLT, n = 14) or bridge-enhanced ACL repair (BEAR, n = 16). We used an isotopically labeled high resolution LC MS/MS-based proteomics approach to analyze the protein profile of synovial fluid at 6 and 12 months after ACL transection in untreated and repaired porcine knees. A linear mixed effect model was used to compare the normalized protein abundance levels between the groups at each time point. Bivariate linear regression analyses were used to assess the correlations between the macroscopic cartilage damage (total lesion area) and normalized abundance levels of each of the identified secreted proteins. There were no significant differences in cartilage lesion area or quantitative abundance levels of the secreted proteins between the ACLT and BEAR groups at 6 months. However, by 12 months, greater cartilage damage was seen in the ACLT group compared to the BEAR group (p = 0.005). This damage was accompanied by differences in the abundance levels of secreted proteins, with higher levels of Vitamin K-dependent protein C (p = 0.001), and lower levels of Apolipoprotein A4 (p = 0.021) and Cartilage intermediate layer protein 1 (p = 0.049) in the ACLT group compared to the BEAR group. There were also group differences in the secreted proteins that significantly changed in abundance between 6 and 12 months in ACLT and BEAR knees. Increased concentration of Ig lambda-1 chain C regions and decreased concentration of Hemopexin, Clusterin, Coagulation factor 12 and Cartilage intermediate layer protein 1 were associated with greater cartilage lesion area. In general, ACLT knees had higher concentrations of pro-inflammatory proteins and lower concentrations of anti-inflammatory proteins than BEAR group. In addition, the ACLT group had a lower and declining synovial concentrations of CILP, in contrast to a consistently high abundance of CILP in repaired knees. These differences suggest that the knees treated with bridge-enhanced ACL repair may be maintaining an environment that is more protective of the extracellular matrix, a function which is not seen in the ACLT knees.


Assuntos
Cartilagem Articular/metabolismo , Traumatismos do Joelho/metabolismo , Articulação do Joelho/metabolismo , Osteoartrite do Joelho/metabolismo , Proteoma/metabolismo , Membrana Sinovial/metabolismo , Animais , Cartilagem Articular/patologia , Traumatismos do Joelho/complicações , Traumatismos do Joelho/patologia , Articulação do Joelho/patologia , Osteoartrite do Joelho/etiologia , Osteoartrite do Joelho/patologia , Suínos , Porco Miniatura , Membrana Sinovial/patologia
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