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1.
BMC Musculoskelet Disord ; 23(1): 604, 2022 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-35733134

RESUMO

BACKGROUND: Tryptophan 2,3-dioxygenase (TDO2) is the primary enzyme that catabolizes tryptophan to kynurenine. Numerous studies have suggested that TDO2 is involved in inflammation-related diseases. However, its role in osteoarthritis (OA) has not yet been investigated. The aim of the present study was to explore the levels of TDO2 in the synovium and synovial fluid (SF) of patients with OA and its correlation with clinical manifestations and levels of pro-inflammatory cytokines.  METHODS : Synovium and SF samples were collected from patients with OA and patients with joint trauma (controls) during surgery. An enzyme-linked immunosorbent assay (ELISA) was used to measure TDO2, interleukin-1ß (IL-1ß), and tumor necrosis factor-α (TNF-α) levels in the synovium and SF. Diagnostic performance of TDO2 in the synovium to discriminate between controls and OA patients was assessed using receiver operating characteristic (ROC) curve analysis. Correlations between TDO2 levels, OA clinical features, and pro-inflammatory cytokines were evaluated using Pearson correlation analysis. Effects of IL-1ß or TNF-α stimulation on TDO2 expression in OA-fibroblast-like synoviocytes (OA-FLS) were also examined. RESULTS: The levels of TDO2, IL-1ß, and TNF-α in the synovium of patients with OA were found to be significantly higher than those in controls. ROC curve analysis revealed an area under the curve (AUC) of 0.800 with 64.3% sensitivity and 85.0% specificity of TOD2 in the synovium, which enabled discriminating patients with OA from controls. Moreover, protein expression of TDO2 was upregulated to a greater extent in OA-FLS than in normal synovial fibroblasts (NSF). Furthermore, the levels of TDO2 showed significantly positive correlation with IL-1ß and TNF-α levels in the synovium and SF. TDO2 levels in the synovium were also positively correlated with the Kellgren-Lawrence score. Additionally, TDO2 protein expression was significantly increased in IL-1ß‒ or TNF-α‒stimulated OA-FLS than in control FLS. CONCLUSION: These data indicate that highTDO2 levels in the synovium can be correlated with pro-inflammatory cytokines and severity of OA.


Assuntos
Osteoartrite , Líquido Sinovial , Triptofano Oxigenase , Células Cultivadas , Citocinas/metabolismo , Fibroblastos , Humanos , Osteoartrite/patologia , Líquido Sinovial/metabolismo , Membrana Sinovial/patologia , Triptofano Oxigenase/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
2.
Front Cell Infect Microbiol ; 12: 875822, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35755833

RESUMO

Background: A prosthetic joint infection (PJI) is a devastating complication following total joint arthroplasties with poor prognosis. Identifying an accurate and prompt diagnostic method is particularly important for PJI. Recently, the diagnostic value of metagenomic next-generation sequencing (mNGS) in detecting PJI has attracted much attention, while the evidence of its accuracy is quite limited. Thus, this study aimed to evaluate the accuracy of mNGS for the diagnosis of PJI. Methods: We summarized published studies to identify the potential diagnostic value of mNGS for PJI patients by searching online databases using keywords such as "prosthetic joint infection", "PJI", and "metagenomic sequencing". Ten of 380 studies with 955 patients in total were included. The included studies provided sufficient data for the completion of 2-by-2 tables. We calculated the sensitivity, specificity, and area under the SROC curve (AUC) to evaluate mNGS for PJI diagnosis. Results: We found that the pooled diagnostic sensitivity and specificity of mNGS for PJI were 0.93 (95% CI, 0.83 to 0.97) and 0.95 (95% CI, 0.92 to 0.97), respectively. Positive and negative likelihood ratios were 18.3 (95% CI, 10.9 to 30.6) and 0.07 (95% CI, 0.03 to 0.18), respectively. The area under the curve was 0.96 (95% CI, 0.93 to 0.97). Conclusion: Metagenomic next-generation sequencing displays high accuracy in the diagnosis of PJI, especially for culture-negative cases.


Assuntos
Artrite Infecciosa , Infecções Relacionadas à Prótese , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Metagenômica/métodos , Infecções Relacionadas à Prótese/diagnóstico , Sensibilidade e Especificidade , Líquido Sinovial
3.
Adv Rheumatol ; 62(1): 21, 2022 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-35725524

RESUMO

OBJECTIVES: To describe the feature of expression of syndecan-4 in serum, synovial fluid (SF) and synovium in rheumatoid arthritis (RA) patients, and to analyze the correlation of syndecan-4 with disease activity and serological characteristic of RA. METHODS: Syndecan-4 in sera of 60 RA patients, 20 osteoarthritis (OA) patients, 20 healthy controls, and in SF of 25 RA patients and 25 OA patients were tested by enzyme linked immunosorbant assay. The expressions of syndecan-4 in synovium of RA and OA patients were detected by immunohistochemistry. The expression of syndecan-4 on synovial fibroblasts from RA and OA patients were detected by immunofluorescence. The correlation between serum syndecan-4 concentration and disease activity were analyzed in RA patients. RESULTS: The serum syndedcan-4 concentration was significantly higher in RA patients than in OA patients and healthy controls, and was higher in rheumatoid factor (RF)-positive RA patients than in RF-negative ones. Syndecan-4 concentration in SF of RA patients was comparable with OA patients. Syndecan-4 expression in synovial tissue was similar between RA and OA patients. The syndecan-4 concentration was significantly lower in SF than in serum of RA and OA patients. Syndecan-4 concentration in both serum and SF was positively correlated with disease activity of RA patients. CONCLUSION: The serum syndecan-4 concentration was higher in RA patients than in OA patients, and significantly higher in RF-positive RA patients than in RF-negative ones. Syndecan-4 concentration in both serum and SF was positively correlated with disease activity of RA patients.


Assuntos
Artrite Reumatoide , Osteoartrite , Sindecana-4 , Artrite Reumatoide/diagnóstico , Humanos , Osteoartrite/diagnóstico , Sindecana-4/metabolismo , Líquido Sinovial , Membrana Sinovial/metabolismo
4.
Front Immunol ; 13: 890094, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35686134

RESUMO

Purpose: Synovial inflammation in knee osteoarthritis (OA) causes disorganized synovial angiogenesis and complement activation in synovial fluid, but links between complement and synovial microvascular pathology have not been established. Since complement causes vascular pathology in other diseases and since sex-differences exist in complement activation and in OA, we investigated sex differences in synovial fluid complement factors, synovial tissue vascular pathology, and associations between complement and synovial vascular pathology in patients with late-stage knee OA. Methods: Patients with symptomatic, late-stage radiographic knee OA undergoing total knee arthroplasty or high tibial osteotomy provided matched synovial fluid and tissue biopsies during surgery. Complement factors (C2, C5, adipsin, MBL, and CFI) and terminal complement complex (sC5b-C9) were measured in synovial fluid by multiplex or enzyme-linked immunosorbent assay, respectively. Features of synovial vascular pathology (vascularization, perivascular edema, and vasculopathy) were assessed by histopathology. Multivariate linear regression models were used to assess associations between synovial fluid complement factors and histopathological features of vascular pathology, with adjustment for age, sex, body mass index, and sex interaction. Sex-disaggregated comparisons were completed. Results: Synovial fluid biomarker and histopathology data were included from 97 patients. Most synovial fluid complement factors and synovial tissue histopathological features were similar between sexes. Synovial fluid C5 trended to lower levels in males (-20.93 ng/mL [95%CI -42.08, 0.23] p=0.05). Median vasculopathy scores (0.42 [95%CI 0.07, 0.77] p=0.02) were higher in males. In the full cohort, C5 concentration was associated with lower vascularization scores (-0.005 [95%CI -0.010, -0.0001] p=0.04) while accounting for sex*C5 interaction. In sex-disaggregated analyses, increased C5 concentration was associated with lower vascularization scores (-0.005 [95%CI -0.009, -0.0001] p=0.04) in male patients, but not in female patients. Males had higher sC5b-C9 compared to females. Additionally, males with high C5 had a higher synovial fluid concentration of sC5b-C9 compared to males with low C5. No differences were found in females. Conclusion: Higher synovial fluid C5 levels were associated with increased complement activation and decreased synovial vascularization in males but not in females with OA. Future studies should test whether synovial fluid complement activation suppresses synovial angiogenesis and identify mechanisms accounting for C5-related sex-differences in synovial fluid complement activation in patients with knee OA.


Assuntos
Osteoartrite do Joelho , Ativação do Complemento , Feminino , Humanos , Masculino , Caracteres Sexuais , Líquido Sinovial , Membrana Sinovial/patologia
5.
BMC Vet Res ; 18(1): 215, 2022 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-35681208

RESUMO

BACKGROUND: Combined chondroitin sulfate (CS) and glucosamine (GlcN) has been widely used in oral formulations to prevent and treat osteoarthritis. CS is effective for controlling pain in osteoarthritic patients, whereas GlcN can stimulate glycosaminoglycan synthesis, thus reducing extracellular matrix degradation. Although several studies have been published on this topic, the effectiveness of treatment with oral CS and GlcN remains uncertain. The objective of this study was to analyze the progression of experimentally induced osteoarthritis in horses and verify the effectiveness of an oral compound based on CS and GlcN to treat and/or modulate this disease. The study analyzed the metacarpophalangeal joint of the left thoracic limb of 16 horses divided into two groups, with eight horses treated with CS and GlcN in the treated group (GT) and eight untreated horses in the control group (GC). Chondral lesions were induced through arthroscopy, which was defined as time-point zero (T0). Physical, ultrasonographic, and radiographic examinations and synovial fluid biomarkers measurements were performed on days 0, 30, 60, 90, and 120. At the end of the experiment (T4), arthroscopy was performed again to macroscopically evaluate the joints and collect material for microscopic analysis. RESULTS: Significant differences were observed between groups in some evaluated parameters, such as visual lameness assessment, synovial concentrations of prostaglandin E2, and ultrasound examination. However, the GT still presented slightly improved results for joint flexion angle, analysis of lameness using sensors, and histopathological analysis of chondral repair tissue, however, without the statistical significance (p>0.05). CONCLUSIONS: The treatment was considered effective in the clinical modulation of experimental osteoarthritis, with improvement of some parameters in the GT. However, this type of treatment may not be entirely effective to change the catabolic process in articular cartilage and the progressive induced chondral damage.


Assuntos
Cartilagem Articular , Doenças dos Cavalos , Osteoartrite , Animais , Cartilagem Articular/patologia , Sulfatos de Condroitina/farmacologia , Sulfatos de Condroitina/uso terapêutico , Glucosamina/farmacologia , Glucosamina/uso terapêutico , Doenças dos Cavalos/metabolismo , Cavalos , Coxeadura Animal/metabolismo , Modelos Teóricos , Osteoartrite/tratamento farmacológico , Osteoartrite/patologia , Osteoartrite/veterinária , Líquido Sinovial/metabolismo
6.
Int J Mol Sci ; 23(11)2022 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-35682922

RESUMO

Matrix metalloproteinases (MMPs) play crucial roles in tissue homeostasis and pathologies by remodeling the extracellular matrix. Previous studies have demonstrated the biological activities of MMP-derived cleavage products. Furthermore, specific fragments can serve as biomarkers. Therefore, an in vitro cleavage assay to identify substrates and characterize cleavage patterns could provide important insight in disease-relevant mechanisms and the identification of novel biomarkers. In the pathogenesis of osteoarthritis (OA), MMP-2, -8, -9 and -13 are of vital importance. However, it is unclear which protease can cleave which matrix component. To address this question, we established an in vitro cleavage assay using recombinantly expressed MMPs and the two cartilage matrix components, COMP and thrombospondin-4. We found a time- and concentration-dependent degradation and an MMP-specific cleavage pattern for both proteins. Cleavage products can now be enriched and purified to investigate their biological activity. To verify the in vivo relevance, we compared the in vitro cleavage patterns with serum and synovial fluid from OA patients and could indeed detect fragments of similar size in the human samples. The cleavage assay can be adapted to other MMPs and substrates, making it a valuable tool for many research fields.


Assuntos
Metaloproteinases da Matriz , Osteoartrite , Biomarcadores/metabolismo , Cartilagem/metabolismo , Proteínas da Matriz Extracelular/metabolismo , Humanos , Metaloproteinases da Matriz/metabolismo , Osteoartrite/metabolismo , Líquido Sinovial/metabolismo
7.
Clin Chim Acta ; 532: 145-163, 2022 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-35667478

RESUMO

Osteoarthritis (OA) is a progressive joint disease that affects millions of older adults around the world. With increasing rates of incidence and prevalence worldwide, OA has become an enormous global socioeconomic burden on healthcare systems. Long non-coding ribonucleic acids (lncRNAs), essential functional molecules in many biological processes, are a group of non-coding RNAs that are greater than approximately 200 nucleotides in length. Fast-growing and recent developments in lncRNA research are captivating and represent a novel and promising field in understanding the complexity of OA pathogenesis. The involvement of lncRNAs in OA's pathological processes and their altered expressions in joint tissues, blood and synovial fluid make them attractive candidates for the diagnosis and treatment of OA. We focus on the recent advances in major regulator mechanisms of lncRNAs in the pathophysiology of OA and discuss potential diagnostic and therapeutic uses of lncRNAs for OA. We investigate how upregulation or downregulation of lncRNAs influences the pathogenesis of OA and how we can use lncRNAs to elucidate the molecular mechanism of OA. Furthermore, we evaluate how we can use lncRNAs as a diagnostic marker or therapeutic target for OA. Our study not only provides a comprehensive review of lncRNAs regarding OA's pathogenesis but also contributes to the elucidation of its molecular mechanisms and to the development of diagnostic and therapeutic approaches for OA.


Assuntos
Osteoartrite , RNA Longo não Codificante , Idoso , Humanos , Osteoartrite/diagnóstico , Osteoartrite/genética , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Líquido Sinovial/metabolismo , Regulação para Cima
8.
Biomed Pharmacother ; 152: 113181, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35653890

RESUMO

Several mediators including cytokines, growth factors and metalloproteinases (MMP) modulate pathological angiogenesis associated with inflammatory arthritis. The biological factors underlying sex disparities in the incidence and severity of rheumatic musculoskeletal diseases are only partially understood. We hypothesized that synovial fluids (SFs) from rheumatoid arthritis (RA) and psoriatic arthritis (PsA) patients would impact on endothelial biology in a sexually dimorphic fashion. Immune cell counts and levels of pro-angiogenic cytokines found in SFs from RA and PsA patients (n = 17) were higher than in osteoarthritis patients (n = 6). Synovial VEGF concentration was significantly higher in male than in female RA patients. Zymography revealed that SFs comprised solely MMP-9 and MMP-2, with significantly higher MMP-9 levels in male than female RA patients. Using in vitro approaches that mimic the major steps of the angiogenic process, SFs from RA and PsA patients induced endothelial migration and formation of capillary-like structures compared to control. Notably, endothelial cells from female donors displayed enhanced angiogenic response to SFs with respect to males. Treatment with the established anti-angiogenic agent digitoxin prevented activation of focal adhesion kinase and SF-induced in vitro angiogenesis. Thus, despite higher synovial VEGF and MMP-9 levels in male patients, the responsiveness of vascular endothelium to SF priming was higher in females, suggesting that gender differences in angiogenic responses were mainly related to the endothelial genotype. These findings may have implications for pathogenesis and targeted therapies of inflammatory arthritis.


Assuntos
Artrite Psoriásica , Artrite Reumatoide , Artrite Psoriásica/tratamento farmacológico , Artrite Psoriásica/metabolismo , Artrite Psoriásica/patologia , Artrite Reumatoide/metabolismo , Citocinas/metabolismo , Células Endoteliais/metabolismo , Feminino , Humanos , Masculino , Metaloproteinase 9 da Matriz/metabolismo , Neovascularização Patológica/metabolismo , Fatores Sexuais , Líquido Sinovial/metabolismo , Membrana Sinovial/patologia , Fator A de Crescimento do Endotélio Vascular/metabolismo
9.
J Vis Exp ; (184)2022 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-35723474

RESUMO

In primary osteoarthritis (OA), normal 'wear and tear' associated with aging inhibits the ability of cartilage to sustain its load-bearing and lubrication functions, fostering a deleterious physical environment. The frictional interactions of articular cartilage and synovium may influence joint homeostasis through tissue level wear and cellular mechanotransduction. To study these mechanical and mechanobiological processes, a device capable of replicating the motion of the joint is described. The friction testing device controls the delivery of reciprocal translating motion and normal load to two contacting biological counterfaces. This study adopts a synovium-on-cartilage configuration, and friction coefficient measurements are presented for tests performed in a phosphate-buffered saline (PBS) or synovial fluid (SF) bath. The testing was performed for a range of contact stresses, highlighting the lubricating properties of SF under high loads. This friction testing device can be used as a biomimetic bioreactor for studying the physical regulation of living joint tissues in response to applied physiologic loading associated with diarthrodial joint articulation.


Assuntos
Cartilagem Articular , Mecanotransdução Celular , Fenômenos Biomecânicos , Biofísica , Reatores Biológicos , Cartilagem Articular/fisiologia , Fricção , Lubrificação , Estresse Mecânico , Líquido Sinovial
10.
PLoS One ; 17(6): e0268198, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35675298

RESUMO

The inflammatory response to joint injury has been thought to play a key role in the development of osteoarthritis. In this preclinical study, we hypothesized that synovial fluid presence of inflammatory cytokines, as well as altered loading on the injured leg, would be associated with greater development of macroscopic cartilage damage after an ACL injury. Thirty-six Yucatan minipigs underwent ACL transection and were randomized to: 1) no further treatment, 2) ACL reconstruction, or 3) scaffold-enhanced ACL restoration. Synovial fluid samples and gait data were obtained pre-operatively and at multiple time points post-operatively. Cytokine levels were measured using a multiplex assay. Macroscopic cartilage assessments were performed following euthanasia at 52 weeks. General estimating equation modeling found the presence of IL-1α, IL-1RA, IL-2, IL-4, IL-6, and IL-10 and MMP-2, MMP-3, MMP-12, and MMP-13 in the synovial fluid was associated with better cartilage outcomes. Higher peak pressure for the surgical hind leg and contralateral hind leg aligned with worse cartilage outcomes. A support vector machine built with synovial fluid and gait metrics also demonstrated cytokine presence was predictive of better cartilage outcomes. In conclusion, this preclinical analysis suggests that synovial fluid devoid of cytokines may be a possible indicator that cartilage is more at risk of becoming pathologic after joint injury.


Assuntos
Lesões do Ligamento Cruzado Anterior , Cartilagem Articular , Animais , Lesões do Ligamento Cruzado Anterior/patologia , Lesões do Ligamento Cruzado Anterior/cirurgia , Cartilagem , Cartilagem Articular/patologia , Marcha , Máquina de Vetores de Suporte , Suínos , Porco Miniatura , Líquido Sinovial
11.
Mediators Inflamm ; 2022: 2606916, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35693109

RESUMO

Background: Rheumatoid arthritis (RA) and osteoarthritis (OA) are common joint diseases associated with changes in local, as well as systemic bone structure and osteoclast function. We investigated how the different soluble inflammatory stimuli in these diseases can affect osteoclastogenesis and bone resorption in vitro. Methods. Human peripheral blood mononuclear cell-derived osteoclasts were cultured on bone slices with serum from treatment-naïve RA patients and healthy controls and with synovial fluid samples acquired from RA and OA patients. The concentrations of 29 different cytokines and related proteins, including RANKL and OPG, were analyzed in the fluids tested. Results: RA serum and synovial fluid increased both osteoclastogenesis and bone resorption. Osteoclastogenesis and activity increased more in the cultures containing OA than RA synovial fluid. The osteoclasts cultured in different culture media exhibited different phenotypes, especially the cells cultured with OA synovial fluid were generally larger and had more nuclei. A general increase in proinflammatory cytokines in RA synovial fluid and serum was found. Surprisingly, OA synovial fluid showed lower levels of osteoclastogenesis inhibiting cytokines, such as IL-4 and IL-10, than RA synovial fluid, which at least partly explains more pronounced osteoclastogenesis. No significant difference was found in RANKL or OPG levels. Conclusion: The proinflammatory stimulus in OA and RA drives the monocyte differentiation towards inflammatory osteoclastogenesis and altered osteoclast phenotype.


Assuntos
Artrite Reumatoide , Reabsorção Óssea , Osteoartrite , Artrite Reumatoide/metabolismo , Reabsorção Óssea/metabolismo , Citocinas/metabolismo , Humanos , Leucócitos Mononucleares/metabolismo , Monócitos/metabolismo , Osteoartrite/metabolismo , Osteoclastos/metabolismo , Osteogênese , Líquido Sinovial/metabolismo , Membrana Sinovial/metabolismo
12.
Int Orthop ; 46(7): 1473-1479, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35524793

RESUMO

PURPOSE: Diagnosing periprosthetic joint infections (PJI) are challenging and may be hampered by the presence of other causes of local inflammation. Conventional synovial and serum markers are not reliable under these circumstances. Synovial calprotectin has been recently shown as a promising biomarker for PJI in total hip (THA) and total knee arthroplasty (TKA). The aim of this study is to investigate if calprotectin is reliable for PJI diagnosis in cases with accompanying inflammation due to recent surgery, dislocation or implant breakage in primary and revision TKA and THA. METHODS: Thirty-three patients were included in this prospective study between July 2019 and October 2021 (17 patients undergoing surgery < 9 months, 11 dislocations, five implant breakage, respectively). Synovial white blood cell count (WBC), percentage of polymorphonuclear neutrophils (PMC), serum C-reactive protein (CRP) and synovial calprotectin, using a lateral-flow-assay, were analysed. These parameters were tested against a modified European-Bone-and-Joint-Infection-Society (EBJIS) definition with adjusted thresholds to account for the local inflammation. Statistic quality criteria were calculated and compared using a binary classification test. RESULTS: Seventeen patients were classified as confirmed infections according to the modified EBJIS definition (13 THA and 4 TKA). The calprotectin assay yielded a sensitivity of 0.88 (0.64, 0.99), a specificity of 0.81 (0.54, 0.96), a positive predictive value (PPV) of 0.83 (0.59, 0.96) and a negative predictive value (NPV) of 0.87 (0.60, 0.98). CONCLUSIONS: Even in the presence of local inflammation due to other, non-infectious causes, calprotectin is a reliable diagnostic parameter for the detection of a PJI in primary and revision THA and TKA.


Assuntos
Artrite Infecciosa , Artroplastia de Quadril , Infecções Relacionadas à Prótese , Artrite Infecciosa/cirurgia , Artroplastia de Quadril/efeitos adversos , Biomarcadores/análise , Proteína C-Reativa/análise , Humanos , Inflamação/complicações , Complexo Antígeno L1 Leucocitário/análise , Estudos Prospectivos , Infecções Relacionadas à Prótese/cirurgia , Sensibilidade e Especificidade , Líquido Sinovial/metabolismo
13.
Front Immunol ; 13: 863753, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35603149

RESUMO

Objectives: This study aimed to investigate the changes in quantity and function of T helper (Th)-like T regulatory (Treg) cell subsets in peripheral blood (PB) and synovial fluid (SF) of rheumatoid arthritis (RA) patients and to understand their relationship with disease activity. Methods: A total of 86 RA patients and 76 gender and age-matched healthy controls (HC) were enrolled in this study. Th-like Treg frequency and function were determined using flow cytometry. The inhibitory function of Th-like Treg cells was detected using an in vitro co-culture suppression assay. Results: The proportion and absolute number of Th1-like Treg cells from RA PB and RA SF were significantly higher than those of HC PB. In RA SF, the proportions of Treg cells and Th1-like Treg cells were significantly lower in the elevated erythrocyte sedimentation rate or the C-Reactive Protein group, and in the positive groups of anti-CCP antibody and anti-MCV antibody. Additionally, the proportions of Treg cells and Th1-like Treg cells from RA SF were negatively correlated with disease activity. However, the expression levels of CD73 and TGF-ß1 in Th1-like Treg cells were decreased, and these Treg cells could not effectively inhibit the proliferation of effector T (Teff) cells. Conclusion: Our data indicate that Th1-like Treg cells are the predominant Treg cell subset in RA SF, but their suppressive function is defective. Improving the function of Th1-like Treg cells may control inflammation in joints and provide new strategies for Treg-targeted therapies in RA.


Assuntos
Artrite Reumatoide , Linfócitos T Reguladores , Citometria de Fluxo , Humanos , Líquido Sinovial
14.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 38(4): 333-337, 2022 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-35583063

RESUMO

Objective To investigate the effect of inhibitor of differentiation 2 (Id2) on the proportion of CD4+T cells by detecting the proportion of CD4+T cell subsets and Id2 expression in peripheral blood and joint synovial fluid of patients with rheumatoid arthritis (RA). Methods A total of 51 RA patients (including 18 patients providing synovial fluid) and 31 healthy controls (HCs) were enrolled. The proportions of CD4+T cells, Th1 cells, and Th17 cells, and their expression of Id2 in peripheral blood and synovial fluid of RA patients and HCs were detected by flow cytometry. Results Compared with HCs group, the proportions of circulating CD4+T cells, Th1 cells, and Th17 cells and their expression of Id2 in RA patients did not change significantly. The proportions of CD4+T cells and Th1 cells, and Id2 expression in CD4+T cells in synovial fluid of RA patients were significantly higher than those in peripheral blood of RA patients and HCs. The expression rate of Id2 in CD4+T cells was positively correlated with the expression of IFN-γ, but not with erythrocyte sedimentation rate (ESR), C reactive protein (CRP), and Disease Activity Score 28 (DAS28). Conclusion CD4+T cells are enriched in RA synovial fluid, and their Id2 expression may promote Th1 cell differentiation.


Assuntos
Artrite Reumatoide , Proteína 2 Inibidora de Diferenciação , Líquido Sinovial , Artrite Reumatoide/metabolismo , Artrite Reumatoide/patologia , Sedimentação Sanguínea , Diferenciação Celular , Humanos , Proteína 2 Inibidora de Diferenciação/metabolismo , Células Th1
15.
PLoS One ; 17(5): e0268076, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35533148

RESUMO

BACKGROUND: Extracellular vesicles (EVs) are considered as crucial players in a wide variety of biological processes. Although their importance in joint diseases or infections has been shown by numerous studies, much less is known about their function in periprosthetic joint infection (PJI). Our aim was to investigate activated polymorphonuclear (PMN)-derived synovial EVs in patients with PJI. QUESTIONS/PURPOSES: (1) Is there a difference in the number and size of extracellular vesicles between periprosthetic joint aspirates of patients with PJI and aseptic loosening? (2) Are these vesicles morphologically different in the two groups? (3) Are there activated PMN-derived EVs in septic samples evaluated by flow cytometry after CD177 labelling? (4) Is there a difference in the protein composition carried by septic and aseptic vesicles? METHODS: Thirty-four patients (n = 34) were enrolled into our investigation, 17 with PJI and 17 with aseptic prosthesis loosening. Periprosthetic joint fluid was aspirated and EVs were separated. Samples were analysed by nanoparticle tracking analysis (NTA) and transmission electron microscopy (TEM) and flow cytometry (after Annexin V and CD177 labelling). The protein content of the EVs was studied by mass spectrometry (MS). RESULTS: NTA showed particle size distribution in both groups between 150 nm and 450 nm. The concentration of EVs was significantly higher in the septic samples (p = 0.0105) and showed a different size pattern as compared to the aseptic ones. The vesicular nature of the particles was confirmed by TEM and differential detergent lysis. In the septic group, FC analysis showed a significantly increased event number both after single and double labelling with fluorochrome conjugated Annexin V (p = 0.046) and Annexin V and anti-CD177 (p = 0.0105), respectively. MS detected a significant difference in the abundance of lactotransferrin (p = 0.00646), myeloperoxidase (p = 0.01061), lysozyme C (p = 0.04687), annexin A6 (p = 0.03921) and alpha-2-HS-glycoprotein (p = 0.03146) between the studied groups. CONCLUSIONS: An increased number of activated PMN derived EVs were detected in the synovial fluid of PJI patients with a characteristic size distribution and a specific protein composition. The activated PMNs-derived extracellular vesicles can be potential biomarkers of PJI.


Assuntos
Artrite Infecciosa , Artroplastia de Quadril , Vesículas Extracelulares , Infecções Relacionadas à Prótese , Anexina A5/metabolismo , Biomarcadores/metabolismo , Vesículas Extracelulares/metabolismo , Humanos , Infecções Relacionadas à Prótese/metabolismo , Líquido Sinovial/metabolismo
16.
Sci Rep ; 12(1): 8432, 2022 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-35589865

RESUMO

Synovial fluid-derived mesenchymal stem cells (SFMSCs) play important regulatory roles in the physiological balance of the temporomandibular joint. Interleukin (IL)-1ß regulates the biological behavior of SFMSCs; however, the effects of IL-1ß on long noncoding RNA (lncRNA) and mRNA expression in SFMSCs in the temporomandibular joint are unclear. Here, we evaluated the lncRNA and mRNA expression profiles of IL-1ß-stimulated SFMSCs. Using microarrays, we identified 264 lncRNAs (203 upregulated, 61 downregulated) and 258 mRNAs (201 upregulated, 57 downregulated) that were differentially expressed after treatment with IL-1ß (fold changes ≥ 2, P < 0.05). Kyoto Encyclopedia of Genes and Genomes pathway analysis found that one of the most significantly enriched pathways was the NF-κB pathway. Five paired antisense lncRNAs and mRNAs, eight paired enhancer lncRNAs and mRNAs, and nine paired long intergenic noncoding RNAs and mRNAs were predicted to be co-expressed. A network constructed by the top 30 K-score genes was visualized and evaluated. We found a co-expression relationship between RP3-467K16.4 and IL8 and between LOC541472 and IL6, which are related to NF-κB pathway activation. Overall, our results provide important insights into changes in lncRNA and mRNA expression in IL-1ß-stimulated SFMSCs, which can facilitate the identification of potential therapeutic targets.


Assuntos
Células-Tronco Mesenquimais , RNA Longo não Codificante , Perfilação da Expressão Gênica/métodos , Redes Reguladoras de Genes , Humanos , Interleucina-1beta/metabolismo , NF-kappa B/metabolismo , RNA Longo não Codificante/metabolismo , RNA Mensageiro/metabolismo , Líquido Sinovial/metabolismo
17.
BMC Musculoskelet Disord ; 23(1): 470, 2022 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-35590311

RESUMO

BACKGROUND: Septic arthritis of the native shoulder is traditionally diagnosed with the same strategies as knee or hip septic arthritis. However, septic arthritis of the shoulder is frequently a missed or delayed diagnosis. Reliance on aspiration and serum markers has been called into question recently. The purpose of this study was to conduct a systematic review investigating the value of joint aspiration and serum markers in the diagnosis of native shoulder joint sepsis. METHODS: PubMed/MEDLINE, Scopus, and the Cochrane Library were used in the systematic literature search from January 1, 1960, through January 23, 2021. The primary outcome was to report on the synovial white cell count of patients with native shoulder sepsis. Descriptive statistics using percentages, means, and intraclass correlation coefficient (ICC) values were used to summarize the results. RESULTS: Thirty-one studies, including 25 case series, one case-control, and five cohort studies with a total of 7434 native shoulder joints, were included. There was no standardized approach to diagnosing septic arthritis of the shoulder. Only 10 studies (32%) reported on synovial white cell count with the majority yielding aspiration counts greater than 50,000 cells/mm3, although one study was as low as 30,000 cells/mm3. CONCLUSIONS: The diagnosis of native shoulder joint sepsis lacks uniformity. Methods used to evaluate shoulder sepsis are heterogeneous and may lead to delays or misdiagnosis with devastating sequelae. Synovial white cell count is underutilized and may also present with a lower value than expected, which is likely related to the time interval between symptom onset and diagnosis.


Assuntos
Artrite Infecciosa , Sepse , Articulação do Ombro , Artrite Infecciosa/diagnóstico , Biomarcadores , Humanos , Estudos Retrospectivos , Sepse/diagnóstico , Ombro , Líquido Sinovial
18.
Vet Clin North Am Small Anim Pract ; 52(4): 959-966, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35562222

RESUMO

Indications for injecting synovial joints may include diagnostic, therapeutic, or combination. Diagnostic injectates aim to reduce or eliminate the contribution of pain to lameness and may be assessed both subjectively or objectively by the clinician. Diagnostic joint injections are not specific for a disease and their limitations must be remembered when interpreting a response-including false-negative results. Patient selection and sterile technique throughout the procedure minimize adverse effects. Risks of intra-articular (IA) injections may include transient soreness, cartilage damage, and, rarely, septic arthritis. Ultrasound guidance with a trained clinician may provide further benefits including the reduction of periprocedural discomfort, reduction in iatrogenic cartilage damage during needle insertion, and improvement in synovial fluid feedback. The removal of some synovial fluid before administering an IA injection should be considered to confirm needle placement, provide diagnostic sampling, and help accommodate injectate volume.


Assuntos
Articulações , Líquido Sinovial , Animais , Injeções Intra-Articulares/métodos , Injeções Intra-Articulares/veterinária , Ultrassonografia/veterinária
19.
Autoimmun Rev ; 21(7): 103120, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35595051

RESUMO

While physiological levels of IL-7 are essential for T cell proliferation, survival and co-stimulation, its escalated concentration has been associated with autoimmune diseases such as Rheumatoid arthritis (RA). Expression of IL-7 and IL-7R in RA monocytes is linked to disease activity score and TNF transcription. TNF stimulation can modulate IL-7 secretion and IL-7R frequency in myeloid cells, however, only IL-7R transcription levels are downregulated in anti-TNF responsive patients. Elevated levels of IL-7 in RA synovial tissue and fluid are involved in attracting RA monocytes into the inflammatory joints and remodeling them into proinflammatory macrophages and mature osteoclasts. Further, IL-7 amplification of RA Th1 cell differentiation and IFNγ secretion, can directly prime myeloid IL-7R expression and thereby exacerbate IL-7-mediated joint inflammatory and erosive imprints. In parallel, IL-7 accentuates joint angiogenesis by expanding the production of proangiogenic factors from RA macrophages and endothelial cells. In preclinical models, blockade of IL-7 or IL-7R can effectively impair joint inflammation, osteoclast formation, and neovascularization primarily by impeding monocyte and endothelial cell infiltration as well as inhibition of pro-inflammatory macrophage and Th1/Th17 cell differentiation. In conclusion, disruption of IL-7/IL-7R signaling can uniquely intercept the crosstalk between RA myeloid and lymphoid cells in their ability to trigger neovascularization.


Assuntos
Artrite Reumatoide , Interleucina-7 , Artrite Reumatoide/genética , Autoimunidade , Células Endoteliais/metabolismo , Humanos , Interleucina-7/genética , Interleucina-7/metabolismo , Líquido Sinovial/metabolismo , Inibidores do Fator de Necrose Tumoral
20.
J Craniomaxillofac Surg ; 50(5): 432-438, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35491326

RESUMO

The aim of this study was to investigate the effect various mediators in synovial fluid (SF) on the pathogenesis of temporomandibular disorders (TMD) and to evaluate the relationship between clinical and radiological features of temporomandibular joint (TMJ) diseases. Patients who had received SF sample during arthrocentesis because of TMD were included in this study. Clinical and radiological records were evaluated retrospectively. Enzyme-Linked ImmunoSorbent Assay (ELISA) method was used for analysis of aggrecan, adiponectin, resistin, apelin, Vascular Endothelial Growth Factor (VEGF) and Prostaglandin E2 (PGE2) in SFs. 59 joints of 41 patients were included in the study. Anterior disc displacement with reduction (ADDwR) was detected in 22 joints, anterior disc displacement without reduction (ADDwoR) was detected in 29 joints and osteoarthritis (OA) in 8. In OA group, PGE2 level was significantly higher than the other groups (p = 0.029). Aggrecan and PGE2 levels were statistically higher in joints with localized pain (p = 0.030, p = 0.029). The aggrecan level was statistically significant higher in patients who had degenerative changes in radiological examinations (p = 0.044). Resistin was correlated with PGE2 and aggrecan (p = 0.011), and apelin showed positive correlation with VEGF (p˂0.001). The detection of aggrecan and adipokines in SF may be a precursor of degenerative joint disease and it should be taken into account that the presence of localized pain in the joint area may be an early sign of degenerative changes.


Assuntos
Luxações Articulares , Transtornos da Articulação Temporomandibular , Adipocinas , Agrecanas , Apelina , Dinoprostona , Humanos , Luxações Articulares/patologia , Dor , Resistina , Estudos Retrospectivos , Líquido Sinovial/metabolismo , Articulação Temporomandibular/patologia , Transtornos da Articulação Temporomandibular/metabolismo , Fator A de Crescimento do Endotélio Vascular
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