RESUMO
We hypothesized that after synovial injury, collagen V (Col V) expose occult antigens, and Col V autoantibodies develop, indicating the loss of immune tolerance against this molecule, thus leading to damage to mesenchymal-derived cells as well as the extracellular matrix in experimental arthritis. Thus, the present study investigated the effects of oral administration of Col V on the synovium after the development of inflammation in mBSA/CFA-induced arthritis. After fourteen days of intraarticular administration of mBSA, 10 male Lewis rats were orally administered Col V (500 µg/300 µL) diluted in 0.01 N acetic acid (IA-Col V group). The arthritic group (IA group, n = 10) received only intraarticular mBSA. An intra-articular saline injection (20 µL) was given to the control group (CT-Col V, n = 5). IA group presented damaged synovia, the expansion of the extracellular matrix by cellular infiltrate, which was characterized by T and B lymphocytes, and fibroblastic infiltration. In contrast, after Col V oral immunotherapy IA-Col V group showed a significant reduction in synovial inflammation and intense expression of IL-10+ and FoxP3+ cells, in addition to a reduction in Col V and an increase in Col I in the synovia compared to those in the IA group. Furthermore, an increase in IL-10 production was detected after IA-Col V group spleen cell stimulation with Col V in vitro. PET imaging did not differ between the groups. The evaluation of oral treatment with Col V, after mBSA/CFA-induced arthritis in rats, protects against inflammation and reduces synovial tissue damage, through modulation of the synovial matrix, showing an immunotherapeutic potential in inhibiting synovitis.
Assuntos
Artrite Experimental , Colágeno Tipo V , Ratos Endogâmicos Lew , Membrana Sinovial , Animais , Masculino , Administração Oral , Ratos , Artrite Experimental/imunologia , Artrite Experimental/tratamento farmacológico , Artrite Experimental/patologia , Membrana Sinovial/imunologia , Membrana Sinovial/patologia , Colágeno Tipo V/imunologia , Colágeno Tipo V/administração & dosagem , Adjuvante de Freund/administração & dosagem , Imunoterapia/métodos , Interleucina-10 , Fatores de Transcrição Forkhead/metabolismo , Soroalbumina BovinaRESUMO
OBJECTIVES: Investigate whether and which synoviocytes would acquire trained immunity characteristics that could exacerbate joint inflammation following a secondary Staphylococcus aureus infection. METHODS: Lipopolysaccharide (LPS) and S. aureus were separately or double injected (21 days of interval) into the tibiofemoral joint cavity of male C57BL/6 mice. At different time points after these stimulations, mechanical nociception was analyzed followed by the analysis of signs of inflammation and damage in the affected joints. The trained immunity markers, including the glycolytic and mTOR pathway, were analyzed in whole tissue or isolated synoviocytes. A group of mice was treated with Rapamycin, an mTOR inhibitor before LPS or S. aureus stimulation. RESULTS: The double LPS - S. aureus hit promoted intense joint inflammation and damage compared to single joint stimulation, including markers in synoviocyte activation, production of proinflammatory cytokines, persistent nociception, and bone damage, despite not reducing the bacterial clearance. The double LPS - S. aureus hit joints increased the synovial macrophage population expressing CX3CR1 alongside triggering established epigenetic modifications associated with trained immunity events in these cells, such as the upregulation of the mTOR signaling pathway (p-mTOR and HIF1α) and the trimethylation of histone H3. Mice treated with Rapamycin presented reduced CX3CR1+ macrophage activation, joint inflammation, and bone damage. CONCLUSIONS: There is a trained immunity phenotype in CX3CR1+ synovial macrophages that contributes to the exacerbation of joint inflammation and damage during septic arthritis caused by S. aureus.
Assuntos
Lipopolissacarídeos , Macrófagos , Camundongos Endogâmicos C57BL , Infecções Estafilocócicas , Staphylococcus aureus , Serina-Treonina Quinases TOR , Animais , Masculino , Infecções Estafilocócicas/imunologia , Macrófagos/imunologia , Serina-Treonina Quinases TOR/imunologia , Staphylococcus aureus/imunologia , Receptor 1 de Quimiocina CX3C/metabolismo , Membrana Sinovial/imunologia , Membrana Sinovial/patologia , Artrite Infecciosa/imunologia , Artrite Infecciosa/microbiologia , Camundongos , Citocinas/imunologia , Citocinas/metabolismo , Sirolimo/farmacologia , Inflamação/imunologia , Sinoviócitos/imunologia , Sinoviócitos/efeitos dos fármacos , Nociceptividade/efeitos dos fármacos , Imunidade TreinadaRESUMO
BACKGROUND: Osteoarthritis (OA) affects the entire joint, causing structural changes in articular cartilage, subchondral bone, ligaments, capsule, synovial membrane, and periarticular muscles that afflicts millions of people globally, leading to persistent pain and diminished quality of life. The intra-articular use of platelet-rich plasma (PRP) is gaining recognition as a secure therapeutic approach due to its potential regenerative capabilities. However, there is controversial clinical data regarding efficacy of PRP for OA treatment. In this context, gathering scientific evidence on the effects of PRP in treating OA in animal models could provide valuable insights into understanding its impact on aspects like cartilage health, synovial tissue integrity, and the inflammatory process in affected joints. Thus, the objective of this study was to assess the effects of PRP injections on inflammation and histopathological aspects of cartilage and synovium in animal models of OA through a comprehensive systematic review with meta-analysis. METHODS: A electronic search was conducted on Medline, Embase, Web of Science, The Cochrane Library, LILACS, and SciELO databases for relevant articles published until June 2022. A random-effects meta-analysis was employed to synthesize evidence on the histological characteristics of cartilage and synovium, as well as the inflammatory process. The GRADE approach was utilized to categorize the quality of evidence, and methodological quality was assessed using SYRCLE's RoB tool. RESULTS: Twenty-one studies were included in the review, with twelve of them incorporated into the meta-analysis. PRP treatment demonstrated superior outcomes compared to the control group in terms of cartilage histology (very low quality; p = 0.0002), synovium histology (very low quality; p < 0.0001), and reductions in proinflammatory markers, including IL-1 (low quality; p = 0.002), IL-6 (very low quality; p < 0.00001), and TNF-α (very low; p < 0.00001). However, PRP treatment did not yield a significant impact on PDGF-A levels (very low quality; p = 0.81). CONCLUSION: PRP appears capable of reducing proinflammatory markers (IL-1, IL-6, TNF-α) and mitigating cartilage and synovium damage in animals with OA. However, the levels of evidence of these findings are low to very low. Therefore, more rigorous studies with larger samples are needed to improve the quality of evidence. PROSPERO REGISTRATION: CRD42022250314.
Assuntos
Cartilagem Articular , Osteoartrite , Plasma Rico em Plaquetas , Animais , Humanos , Fator de Necrose Tumoral alfa , Interleucina-6 , Qualidade de Vida , Osteoartrite/terapia , Membrana Sinovial , Injeções Intra-Articulares , Cartilagem Articular/patologia , Interleucina-1RESUMO
SUMMARY: The anterior cruciate ligament (ACL) is a ligament that mainly controls the anterior and rotational mobility of the knee joint, and its surface is covered by a synovial membrane with large number of blood vessels. In general, nutritional supply to the ligament is from many capillaries in the adjacent synovium. However, statistical studies of the capillaries distributed to the ACL are insufficient. In this study, we examined cross-sectional histological images of the femoral attachment (femoral level), middle level of the tendon (middle level), and tibial attachment (tibial level) of the ACL and statistically analyzed blood capillary distribution among the three levels. The ACLs of 10 cadavers were divided into 5 equal sections, and 4mm-thick paraffin sections were made at the femoral level, middle level, and tibial level, and then hematoxylin-eosin (HE) staining were performed. The area of each transverse section was measured using Image-J 1.51n (U. S. National Institutes of Health, Bethesda, MD, USA). Fiber bundles of the ACL were relatively small and sparse in cross-sectional area at the femoral level and became larger and denser toward the tibial level. Many blood levels. The synovium at the attachment of ACL covered the surface of the fiber bundle and also penetrated deeply between the fiber bundles. In particular, the blood capillaries were densely distributed in the synovium at the femoral attachment rather than another two levels. Indeed, the number of capillaries were also most abundant in the femoral level. The cross-sectional ACL area at the femoral level is significantly small, however, the blood capillaries were most abundant. Therefore, when the ACL is injured, its reconstruction with preservation of the femoral ligamentous remnant may be clinically useful for remodeling of the grafted tendon.
El ligamento cruzado anterior (LCA) es un ligamento que controla principalmente la movilidad anterior y rotacional de la articulación de la rodilla, y su superficie está cubierta por una membrana sinovial con gran cantidad de vasos sanguíneos. En general, el suministro de nutrientes al ligamento proviene de muchos capilares en la sinovial adyacente. Sin embargo, los estudios estadísticos de los capilares distribuidos en el LCA son insuficientes. En este estudio, examinamos imágenes histológicas trans- versales de la inserción femoral (nivel femoral), el nivel medio del tendón (nivel medio) y la inserción tibial (nivel tibial) del LCA y analizamos estadísticamente la distribución de los capilares sanguíneos entre los tres niveles. Los LCA de 10 cadáveres se dividieron en 5 secciones iguales y se realizaron cortes en parafina de 4 µm de espesor a nivel femoral, medio y tibial, y luego se realizó tinción con hematoxilina-eosina (HE). El área de cada sección transversal se midió utilizando Image-J 1.51n (Institutos Nacionales de Salud de EE. UU., Bethesda, MD, EE. UU.). Los haces de fibras del LCA eran relativamente pequeños y escasos en el área de la sección transversal a nivel femoral y se hicieron más grandes y más densos hacia el nivel tibial. La membrana sinovial en la unión del LCA cubría la superficie del haz de fibras y también penetraba profundamente entre entre los haces de fibras. En particular, los capilares sanguíneos estaban densamente distribuidos en la unión femoral de la sinovial respecto a los otros dos niveles. De hecho, el número de capilares también fue más abundante a nivel femoral. El área transversal del LCA a nivel femoral era significativamente pequeña, sin embargo, los capilares sanguíneos fueron los más abundantes. Por lo tanto, cuando hay una lesión del LCA su reconstrucción con preservación del ligamento femoral remanente puede ser clínicamente útil para remodelar el tendón injertado.
Assuntos
Humanos , Masculino , Feminino , Idoso , Idoso de 80 Anos ou mais , Capilares/anatomia & histologia , Ligamento Cruzado Anterior/irrigação sanguínea , Fêmur/irrigação sanguínea , Membrana Sinovial/irrigação sanguínea , Tíbia/irrigação sanguínea , CadáverRESUMO
Osteopontin (OPN) is a bone-derived phosphoglycoprotein related to physiological and pathological mechanisms that nowadays has gained relevance due to its role in the immune system response to chronic degenerative diseases, including rheumatoid arthritis (RA) and osteoarthritis (OA). OPN is an extracellular matrix (ECM) glycoprotein that plays a critical role in bone remodeling. Therefore, it is an effector molecule that promotes joint and cartilage destruction observed in clinical studies, in vitro assays, and animal models of RA and OA. Since OPN undergoes multiple modifications, including posttranslational changes, proteolytic cleavage, and binding to a wide range of receptors, the mechanisms by which it produces its effects, in some cases, remain unclear. Although there is strong evidence that OPN contributes significantly to the immunopathology of RA and OA when considering it as a common denominator molecule, some experimental trial results argue for its protective role in rheumatic diseases. Elucidating in detail OPN involvement in bone and cartilage degeneration is of interest to the field of rheumatology. This review aims to provide evidence of the OPN's multifaceted role in promoting joint and cartilage destruction and propose it as a common denominator of AR and OA immunopathology.
Assuntos
Artrite Reumatoide , Osteoartrite , Osteopontina , Animais , Artrite Reumatoide/metabolismo , Artrite Reumatoide/patologia , Osteoartrite/metabolismo , Osteoartrite/patologia , Osteopontina/metabolismo , Membrana Sinovial/metabolismo , HumanosRESUMO
The fibroblast-like synoviocytes (FLS) have a crucial role in the pathogenesis of Rheumatoid Arthritis (RA); however, its precise mechanisms remain partially unknown. The involvement of the fibroblast in activating adjuvant-induced arthritis (AA) has not been previously reported. The objective was to describe the participation of footpads' fibroblasts in the critical initial process that drives the AA onset. Wistar rats were injected with Complete Freund's Adjuvant (CFA) or saline solution in the hind paws' footpads and euthanized at 24 or 48 h for genetic and histological analyses. Microarrays revealed the differentially expressed genes between the groups. The CFA dysregulated RA-linked biological processes at both times. Genes of MAPK, Jak-STAT, HIF, PI3K-Akt, TLR, TNF, and NF-κB signaling pathways were altered 24 h before the arrival of immune cells (CD4, CD8, and CD68). Key markers TNF-α, IL-1ß, IL-6, NFκB, MEK-1, JAK3, Enolase, and VEGF were immunodetected in fibroblast in CFA-injected footpads at 24 h but not in the control group. Moreover, fibroblasts in the CFA inoculation site overexpressed cadherin-11, which is linked to the migration and invasion ability of RA-FLS. Our study shows that CFA induced a pathological phenotype in the fibroblast of the inoculation site at very early AA stages from 24 h, suggesting a prominent role in arthritis activation processes.
Assuntos
Artrite Experimental , Artrite Reumatoide , Sinoviócitos , Ratos , Animais , Sinoviócitos/metabolismo , Membrana Sinovial/patologia , Adjuvante de Freund , Fosfatidilinositol 3-Quinases/metabolismo , Ratos Wistar , Artrite Experimental/metabolismo , NF-kappa B/metabolismo , Fibroblastos/metabolismoRESUMO
Lameness is a common condition in dairy cattle caused by infectious or noninfectious agents. Joint lesions are the second most common cause of lameness and can be diagnosed in association with the presentation of digit injuries. Fibroblast-like synoviocyte (FLS) are predominant cells of synovia and play a key role in the pathophysiology of joint diseases, thus increasing the expression of proinflammatory mediators. Tumor necrosis factor-alpha (TNF-α) is a potent proinflammatory cytokine involved in cyclooxygenase 2 (COX-2) and proinflammatory cytokine expression in FLS. Previously, TNF-α was demonstrated to increase hypoxia-inducible Factor 1 (HIF-1), a transcription factor that rewires cellular metabolism and increases the expression of interleukin (IL)-6 in bovine FLS (bFLS). Despite this, the proinflammatory effects of TNF-α in bFLS on metabolic reprogramming have been poorly studied. We hypothesized that TNF-α increases glycolysis and in this way controls the expression of IL-6, IL-8, and COX-2 in bFLS. Results first, gas chromatography/mass spectrometry (GC/MS)-based untargeted metabolomics revealed that bTNF-α altered the metabolism of bFLS, increasing glucose, isoleucine, leucine, methionine, valine, tyrosine, and lysine and decreasing malate, fumarate, α-ketoglutarate, stearate, palmitate, laurate, aspartate, and alanine. In addition, metabolic flux analysis using D-glucose-13C6 demonstrated an increase of pyruvate and a reduction in malate and citrate levels, suggesting a decreased flux toward the tricarboxylic acid cycle after bTNF-α stimulation. However, bTNF-α increased lactate dehydrogenase subunit A (LDHA), IL-6, IL-8, IL-1ß and COX-2 expression, which was dependent on glycolysis and the PI3K/Akt pathway. The use of FX11 and dichloroacetate (DCA), an inhibitor of LDHA and pyruvate dehydrogenase kinase (PDK) respectively, partially reduced the expression of IL-6. Our results suggest that bTNF-α induces metabolic reprogramming that favors glycolysis in bFLS and increases IL-6, IL-8, IL-1ß and COX-2/PGE2.
Assuntos
Artrite Reumatoide , Sinoviócitos , Bovinos , Animais , Sinoviócitos/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Interleucina-6/metabolismo , Membrana Sinovial/patologia , Dinoprostona/metabolismo , Interleucina-8/metabolismo , Malatos/metabolismo , Artrite Reumatoide/patologia , Ciclo-Oxigenase 2/metabolismo , Coxeadura Animal , Fosfatidilinositol 3-Quinases/metabolismo , Citocinas/metabolismo , Células Cultivadas , Fibroblastos/metabolismoRESUMO
Synovial chondromatosis of the temporomandibular joint (TMJ) is a rare disease characterized by cartilaginous metaplasia of the mesenchymal remnants of the synovial membrane with formation of loose cartilaginous nodules. It is prevalent in middle-aged women and the main clinical characteristics are swelling, pain, and limited jaw movements. Diagnosis is difficult, especially in the early stages, because the signs and symptoms are like other TMJ diseases such as internal derangements and tumors. Imaging exams are fundamental in differential diagnosis for detection of synovitis and free cartilaginous bodies. Magnetic resonance imaging with a gadolinium contrast would be of particular interest for this purpose. Treatment involves the removal of the cartilaginous nodules and synovectomy. It can be performed by arthroscopy or arthrotomy depending on the size of the lesion, the number of corpuscles, and the need for auxiliary surgical procedures. Final diagnosis is anatomopathologic. Postoperative follow-up is necessary due to the risk of recurrence.
Assuntos
Condromatose Sinovial , Transtornos da Articulação Temporomandibular , Pessoa de Meia-Idade , Humanos , Feminino , Condromatose Sinovial/diagnóstico por imagem , Condromatose Sinovial/cirurgia , Condromatose Sinovial/patologia , Tomografia Computadorizada por Raios X , Articulação Temporomandibular/patologia , Transtornos da Articulação Temporomandibular/diagnóstico por imagem , Transtornos da Articulação Temporomandibular/cirurgia , Transtornos da Articulação Temporomandibular/patologia , Membrana Sinovial , Imageamento por Ressonância MagnéticaRESUMO
Allogeneic mesenchymal stem cells (MSC) are widely used in clinical routine due to the shorter expansion time and reliability of its quality. However, some recipients can produce alloantibodies that recognize MSCs and activate the immune system, resulting in cell death. Although antibody production was already described after MSC injection, no previous studies described the immune response after intra-articular MSC injection in acute synovitis. This study aimed to evaluate the influence of inflammation on immune response after single and repeated intra-articular injections of synovial membrane MSC (SMMSC). Horses were divided in three groups: control group (AUTO) received autologous synovial membrane MSCs; whereas group two (ALLO) received allogeneic SMMSCs and group three (ALLO LPS) was submitted to acute experimental synovitis 8 h before SMMSCs injection. The procedure was repeated for all groups for 28 days. Physical and lameness evaluations and synovial fluid analysis were performed. Sera from all animals were obtained before and every 7 days after each injection up to 4 weeks, to perform microcytotoxicity assays incubating donor SMMSCs with recipients' sera. The first injection caused a mild and transient synovitis in all groups, becoming more evident and longer in ALLO and ALLO LPS groups after the second injection. Microcytotoxicity assays revealed significant antibody production as soon as 7 days after SMMSC injection in ALLO and ALLO LPS groups, and cytotoxicity scores of both groups showed no differences at any time point, being equally different from AUTO group. Although inflammation is capable of inducing MHC expression in MSCs, which enhances immune recognition, cytotoxicity scores were equally high in ALLO and ALLO LPS groups, making it difficult to determine the potentiation effect of inflammation on antibody production. Our findings suggest that inflammation does not display a pivotal role in immune recognition on first allogeneic MSC injection. In a translational way, since specific antibodies were produced against MSCs, patients that need more than one MSC injection may benefit from a first allogeneic injection followed by subsequent autologous injections.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Sinovite , Animais , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Cavalos , Humanos , Inflamação/complicações , Injeções Intra-Articulares/efeitos adversos , Lipopolissacarídeos , Transplante de Células-Tronco Mesenquimais/métodos , Reprodutibilidade dos Testes , Membrana Sinovial , Sinovite/induzido quimicamente , Sinovite/terapiaRESUMO
Rheumatoid arthritis (RA) is a chronic autoimmune disease characterised by symmetric inflammatory polyarthritis. However, RA limited to a single joint is extremely rare. Here, we report a middle-aged woman who presented with insidious right elbow arthritis. She had no other peripheral joint pain, tenderness or swelling. She had high-positive anti-cyclic citrullinated peptide antibodies. An MRI of the right elbow showed capsular distension, joint effusion and bone marrow oedema. Synovial biopsy revealed hyperplasia with lymphoplasmacytic infiltrate consistent with RA. Therapy with methotrexate 7.5 mg orally weekly was effective to control her inflammatory arthritis. This case highlights the relevance of synovial tissue analysis for patients presenting with chronic inflammatory monarthritis when the cause is not clinically evident, and the importance of considering RA even in the absence of polyarticular involvement. Delayed diagnosis and treatment of inflammatory monarthritis can lead to joint destruction and disability.
Assuntos
Artrite Reumatoide , Articulação do Cotovelo , Artrite Reumatoide/complicações , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/tratamento farmacológico , Autoanticorpos , Cotovelo/patologia , Articulação do Cotovelo/diagnóstico por imagem , Articulação do Cotovelo/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Membrana Sinovial/patologiaRESUMO
BACKGROUND: The present review is focused on general aspects of the synovial membrane as well as specialized aspects of its cellular constituents, particularly the composition and location of synovial membrane mesenchymal stem cells (S-MSCs). S-MSC multipotency properties are currently at the center of translational medicine for the repair of multiple joint tissues, such as articular cartilage and meniscus lesions. METHODS AND RESULTS: We reviewed the results of in vitro and in vivo research on the current clinical applications of S-MSCs, surface markers, cell culture techniques, regenerative properties, and immunomodulatory mechanisms of S-MSCs as well as the practical limitations of the last twenty-five years (1996 to 2021). CONCLUSIONS: Despite the poor interest in the development of new clinical trials for the application of S-MSCs in joint tissue repair, we found evidence to support the clinical use of S-MSCs for cartilage repair. S-MSCs can be considered a valuable therapy for the treatment of repairing joint lesions.
Assuntos
Cartilagem Articular , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Diferenciação Celular , Transplante de Células-Tronco Mesenquimais/métodos , Membrana SinovialRESUMO
The synovial membrane (SM) presents itself with distinctive characteristics during arthroscopic procedures in cases of osteoarthritis (OA) as well as osteochondritis dissecans (OCD) in horses. Most of the arthroscopic findings of the SM are limited to a description of a nonspecific inflammation state. In the present study, the macroscopic and histological aspects of the SM in OA and OCD horses were compared to those of healthy horses. The expression of interleukin (IL) in SM was also investigated. Besides, the concentrations of ILs and keratan sulfate (KS) in the synovial fluid (SF), and the molecular weights of the SF hyaluronic acid (HA) were also determined and correlated to the macroscopic and histological aspects of SM. This study included 10 healthy horses (control group), 12 horses with OA, and 12 with OCD. Macroscopic scores of the SM were higher in the OA group in comparison to the control and OCD groups. However, histological scores between OA and OCD were not different, and both were higher than the control group. Only in the OA group, there was a correlation between macroscopic and histological aspects of the SM, especially between volume and quantity of villi with perivascular inflammatory cells and synovial proliferation. The OA group has shown decreased expression of IL-10 in the SM, lower IL-10 and KS, and higher IL-1ß and IL-6 in the SF in comparison to the control and OCD groups. There was a significant negative correlation between the macroscopic aspect of the SM and the molecular weights AH in the OA group. There was no correlation between the macroscopic aspect of the SM and all dosages in the OA and OCD group. In the OA joints, the evaluation of the shape of the SM during arthroscopy promotes a better indicator for joint inflammatory or tissue repair processes, while in the osteochondritic joints, investigation of the histological aspects are recommended to rule out an incipient OA development process. Both are helpful and should be considered to guide the postoperative treatment.
Assuntos
Doenças dos Cavalos , Artropatias , Animais , Biomarcadores , Cavalos , Artropatias/veterinária , Líquido Sinovial , Membrana SinovialRESUMO
Rheumatoid arthritis (RA) is an autoimmune disease characterized by inflammation in the joints. Although methotrexate (MX) is the first-line treatment, side effects are common. This study aimed to investigate the effects of quercetin (QT) and/or MX on inflammation and systemic toxicity in a rat model of RA. Male Wistar rats were divided into control (C), RA, QT, MX, and QT + MX groups (n=6). The RA induction consisted of three intra-articular injections of methylated bovine serum albumin (1×/week) in the temporomandibular joint (TMJ). QT (25 mg/kg) and/or MX (0.75 mg) administration occurred by oral gavage daily. We performed mechanical hyperalgesia in TMJ, leukocyte recruitment in synovial fluid, histopathology, and immunohistochemistry (TNF-α, IL-17, and IL-10) in synovial membrane and toxicity parameters. The RA showed a reduction in the nociceptive threshold (p<0.001), increase in leukocyte recruitment in synovial fluid (p<0.001), intense inflammatory infiltrate (p<0.001), and intense immunoexpression of TNF-α, IL-17, and IL-10 in the synovial membrane (p<0.001) compared to C (p<0.001). QT and/or MX therapy reduced inflammatory parameters (p<0.001). However, downregulation of IL-10 was observed only in the groups that received MX (p<0.001). Leukocytosis was seen in RA (p<0.05), but QT and/or MX reversed it (p<0.05). MX was associated with pathological changes in the liver and higher levels of transaminases when compared to the other groups (p<0.05). QT co-administered with MX reversed this hepatotoxicity (p<0.05). There were no alterations in the kidney between the groups (p>0.05). QT has potential to support MX therapy, showing anti-inflammatory and hepatoprotective effects in this model.
Assuntos
Anti-Inflamatórios/uso terapêutico , Antioxidantes/uso terapêutico , Artrite Experimental/prevenção & controle , Fígado/efeitos dos fármacos , Quercetina/uso terapêutico , Soroalbumina Bovina/toxicidade , Animais , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Artrite Experimental/induzido quimicamente , Artrite Experimental/metabolismo , Hiperalgesia/induzido quimicamente , Hiperalgesia/metabolismo , Hiperalgesia/prevenção & controle , Fígado/metabolismo , Masculino , Quercetina/farmacologia , Ratos , Ratos Wistar , Membrana Sinovial/efeitos dos fármacos , Membrana Sinovial/metabolismo , Resultado do TratamentoRESUMO
The joint disease called pararamosis is an occupational disease caused by accidental contact with bristles of the caterpillar Premolis semirufa. The chronic inflammatory process narrows the joint space and causes alterations in bone structure and cartilage degeneration, leading to joint stiffness. Aiming to determine the bristle components that could be responsible for this peculiar envenomation, in this work we have examined the toxin composition of the caterpillar bristles extract and compared it with the differentially expressed genes (DEGs) in synovial biopsies of patients affected with rheumatoid arthritis (RA) and osteoarthritis (OA). Among the proteins identified, 129 presented an average of 63% homology with human proteins and shared important conserved domains. Among the human homologous proteins, we identified seven DEGs upregulated in synovial biopsies from RA or OA patients using meta-analysis. This approach allowed us to suggest possible toxins from the pararama bristles that could be responsible for starting the joint disease observed in pararamosis. Moreover, the study of pararamosis, in turn, may lead to the discovery of specific pharmacological targets related to the early stages of articular diseases.
Assuntos
Artrite Reumatoide/epidemiologia , Artropatias/epidemiologia , Lepidópteros/patogenicidade , Osteoartrite/epidemiologia , Toxinas Biológicas/toxicidade , Animais , Artrite Reumatoide/induzido quimicamente , Humanos , Inflamação/induzido quimicamente , Inflamação/epidemiologia , Artropatias/induzido quimicamente , Artropatias/patologia , Lepidópteros/química , Doenças Profissionais/induzido quimicamente , Doenças Profissionais/epidemiologia , Osteoartrite/induzido quimicamente , Membrana Sinovial/efeitos dos fármacos , Membrana Sinovial/patologia , Toxinas Biológicas/isolamento & purificação , Peçonhas/efeitos adversos , Peçonhas/químicaRESUMO
Pharmacological treatment of osteoarthritis is still inadequate due to the low efficacy of the drugs used. Dexmedetomidine via the intra-articular (i.a.) route might be an option for the treatment of osteoarthritis-associated pain. The present study assessed the analgesic and anti-inflammatory effects of dexmedetomidine administered via the i.a. route in different doses in an experimental model of rat knee osteoarthritis induced with monosodium iodoacetate. Rats were allocated to four groups with 24 animals in each group. The OA (osteoarthritis), DEX-1 (dexmedetomidine in dose of 1µg/kg) and DEX-3 (dexmedetomidine in dose of 3µg/kg) groups were subjected to induction of osteoarthritis through injection of monosodium iodoacetate (MIA) via the i.a. route on the right knee; the control group was not subjected to osteoarthritis induction. Clinical assessment was performed on day 0 (before osteoarthritis induction) and then on days 5, 10, 14, 21 and 28 after induction. Treatment was performed on day 7 via the i.a. route, consisting of dexmedetomidine in doses of 1 and 3 µg/kg, while group OA received 0.9% normal saline. The animals were euthanized on days 7, 14, 21 and 28. Samples of the synovial membrane were collected for histopathological analysis, and the popliteal lymph nodes were collected for measurement of cytokines (interleukin [IL] IL-6, tumor necrosis factor alpha [TNF-α]). Dexmedetomidine (1 and 3 µg/kg) significantly reduced the animals' weight distribution deficit during the chronic-degenerative stage of osteoarthritis and improved the pain threshold throughout the entire experiment. Histological analysis showed that dexmedetomidine did not cause any additional damage to the synovial membrane. The TNF-α levels decreased significantly in the DEX-3 group on day 28 compared with the OA group. Dexmedetomidine reduced pain, as evidenced by clinical parameters of osteoarthritis in rats, but did not have an anti-inflammatory effect on histological evaluation.
Assuntos
Cartilagem Articular/imunologia , Dexmedetomidina/farmacologia , Interleucina-6/imunologia , Osteoartrite/tratamento farmacológico , Membrana Sinovial/imunologia , Fator de Necrose Tumoral alfa/imunologia , Animais , Cartilagem Articular/patologia , Modelos Animais de Doenças , Injeções Intra-Articulares , Masculino , Osteoartrite/induzido quimicamente , Osteoartrite/imunologia , Osteoartrite/patologia , Ratos , Ratos Wistar , Membrana Sinovial/patologiaRESUMO
The presence of intra-articular crystals is detected in different articular pathologies of acute or chronic nature. The aim of this work was to analyze the action of the indium gallium aluminum and phosphorus (InGaAlP) (λ = 670 nm) laser on the synovial membrane present in the knee joint in experimentally induced microcrystalline arthritis in male adult Wistar rats. The animals were divided into three experimental groups (n = 24): control (A), experimentally induced arthritis (B), experimentally induced arthritis+InGaAlP laser therapy (C). The laser treatment was made daily in the patellar region of the right knee after 48 h of the experimental induction. After 7, 14, and 21 days of therapy, the rats were euthanized and the right knees were removed and processed for histomorphometric, immunohistochemical, ultrastructural, and biochemical investigation of the synovium. The number of granulocytes on the 14th and 21st days was higher in B and lower in C and, lastly, in A. The number of fibroblasts on the 14th and 21st days was similar between A and C and below B. The number of blood vessels on the 21st day was higher in B than in the other groups. The positive number of cells for the TUNEL test was higher on the 14th and 21st days in B compared to the others. The percentage of tissue area occupied by birefringent collagen fibers was higher in B on the 21st day than in the others. The ultrastructure of cells showed fibroblast-like morphology in all groups and periods evaluated. The quantification of glycosaminoglycans did not present significant differences between the groups in all the experimental periods. The amount of hydroxyproline was higher in B compared to the other groups on the 14th and 21st days. The content of non-collagen proteins was higher in B on the 21st day in relation to the other groups. Quantification of TNF-α on the 21st day was higher in A and B than in C. For TGF-ß on the 21st day, groups B and C presented similar and higher values than A. For MMP-13, groups A and B presented data similar to and above C. In relation to ADAMT-S4, on the 21st day, groups B and C presented data similar to and lower than A. InGaAlP-670 nm therapy reduced the inflammatory process and tissue injuries of the synovial membrane in comparison to the untreated group, indicating its potential utilization in clinical studies aiming in the recovery of acute arthritis in patients.
Assuntos
Artrite Experimental/cirurgia , Terapia a Laser , Membrana Sinovial/patologia , Membrana Sinovial/efeitos da radiação , Proteína ADAMTS4/metabolismo , Animais , Apoptose/efeitos da radiação , Vasos Sanguíneos/patologia , Vasos Sanguíneos/efeitos da radiação , Cristalização , Articulação do Joelho/patologia , Masculino , Metaloproteinase 13 da Matriz/metabolismo , Ratos Wistar , Membrana Sinovial/ultraestrutura , Fator de Crescimento Transformador beta/metabolismo , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Inflammatory myofibroblastic tumor (IMT) is a lesion of intermediate biological potential with local recurrences and rare metastases found in multiple anatomical locations. We present a case of a pure intraarticular IMT of the knee, a location that has not been previously documented, with genetic confirmation of ALK-CARS fusion detected with next-generation sequencing. A 20-year-old healthy male was admitted to the orthopedic oncology department due to several months of pain and restriction in movement of his left knee. On magnetic resonance imaging, multiple intraarticular nodular lesions were seen. The patient underwent 2 synovectomies within the course of 1 year. The initial biopsy was interpreted as nodular fasciitis. The second biopsy revealed exuberant tissue displaying compact fascicles of spindle cells intermixed with myxoid areas in a background of inflammatory cells, highly suggestive for IMT. Due to the unusual intraarticular location, equivocal ALK immunostaining and the differential diagnosis with nodular fasciitis, we performed targeted next-generation sequencing using Archer FusionPlex Sarcoma panel, which can identify multiple fusions in a single assay. An ALK-CARS fusion was found, supporting the diagnosis of IMT. This report emphasizes the added value of broad molecular analysis in cases with unusual clinical presentation, equivocal immunohistochemistry, and a wide differential diagnosis.
Assuntos
Articulação do Joelho/patologia , Proteínas de Fusão Oncogênica/genética , Neoplasias de Tecidos Moles/diagnóstico , Membrana Sinovial/patologia , Aminoacil-tRNA Sintetases/genética , Quinase do Linfoma Anaplásico/genética , Biópsia , Procedimentos Cirúrgicos de Citorredução , Diagnóstico Diferencial , Fasciite/diagnóstico , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Articulação do Joelho/diagnóstico por imagem , Articulação do Joelho/imunologia , Articulação do Joelho/cirurgia , Imageamento por Ressonância Magnética , Masculino , Neoplasias de Tecidos Moles/genética , Neoplasias de Tecidos Moles/imunologia , Neoplasias de Tecidos Moles/cirurgia , Sinovectomia , Membrana Sinovial/diagnóstico por imagem , Membrana Sinovial/imunologia , Adulto JovemRESUMO
O lipoma arborescente é uma causa incomum de lesão intra-articular que se apresenta como aumento de volume articular indolor, lentamente progressivo, que persiste por muitos anos e é acompanhado por derrames articulares intermitentes. O envolvimento de sítios extra-articulares é incomum, mas pode ocorrer em bainhas tendíneas e bursas. A ressonância magnética é o melhor exame para o diagnóstico, embora a biópsia sinovial possa ser necessária em alguns casos. Relatamos três casos com o objetivo de destacar o espectro clínico da doença, as características da imagem e a resposta ao tratamento imunossupressor.
Lipoma arborescens is an uncommon cause of intra-articular masses that presents as slowly progressive painless swelling of the joint, which persists for many years and is accompanied by intermittent effusions. Extra-articular site(s) involvement is unusual, but can occur in tendon sheaths and bursas. Magnetic resonance imaging is the best diagnostic exam, although synovial biopsy may be necessary. We report three cases in order to highlight the clinical spectrum and imaging features of the disease, so that early diagnosis and appropriate treatment can be given.
Assuntos
Humanos , Masculino , Feminino , Adulto , Sinovite , Traumatismos do Joelho , Lipoma , Artrite , Membrana Sinovial , Imageamento por Ressonância Magnética , Adipócitos , Sinovectomia , ArticulaçõesRESUMO
This study aimed to explore changes in nanoscale elastic modulus of the synovium using atomic force microscopy (AFM) in addition to investigate changes in synovial histomorphology and secretory function in osteoarthritis (OA) in a rat anterior cruciate ligament transection (ACLT) model. Sprague-Dawley rats were randomly assigned to sham control and ACLT OA groups. All right knee joints were harvested at 4, 8, or 12 weeks (W) after surgery for histological assessment of cartilage damage and synovitis in both the anterior and posterior capsules. AFM imaging and nanoscale biomechanical testing were conducted to measure the elastic modulus of the synovial collagen fibrils. Immunohistochemistry was used to visualize the expression of interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α), and matrix metalloproteinase-3 (MMP-3) in the synovium. The OA groups exhibited progressive development of disease in the cartilage and synovium. Histopathological scores of the synovium in the OA groups increased gradually. Significant differences were observed between all OA groups except for the posterior 4W group. The synovial fibril arrangement in all OA groups was significantly disordered. The synovial fibrils in all ACLT OA groups at each time point were stiffer than those in the sham controls. OA rats displayed a significantly higher expression of IL-1ß and MMP3 in the anterior capsule. In summary, synovial stiffening was closely associated with joint degeneration and might be a factor contributing to synovitis and increased production of proinflammatory mediators. Our data provided insights into the role of synovitis, particularly stiffening of the synovium, in OA pathogenesis.
Assuntos
Cartilagem Articular , Osteoartrite , Animais , Ligamento Cruzado Anterior , Módulo de Elasticidade , Masculino , Microscopia de Força Atômica , Ratos , Ratos Sprague-Dawley , Membrana SinovialRESUMO
OBJECTIVE: To investigate the role of IL-33 in gouty arthritis. MATERIAL: 174 Balb/c (wild-type) and 54 ST2-/- mice were used in this study. In vitro experiments were conducted in bone marrow-derived macrophages (BMDMs). Synovial fluid samples from gouty arthritis (n = 7) and osteoarthritis (n = 8) hospital patients were used to measure IL-33 and sST2 levels. METHODS: Gout was induced by injection of monosodium urate (MSU) crystals in the knee joint of mice. Pain was determined using the electronic von Frey and static weight bearing. Neutrophil recruitment was determined by H&E staining, Rosenfeld staining slides, and MPO activity. ELISA was used for cytokine and sST2 measurement. The priming effect of IL-33 was determined in BMDM. RESULTS: Synovial fluid of gout patients showed higher IL-33 levels and neutrophil counts than osteoarthritis patients. In mice, the absence of ST2 prevented mechanical pain, knee joint edema, neutrophil recruitment to the knee joint, and lowered IL-1ß and superoxide anion levels. In macrophages, IL-33 enhanced the release of IL-1ß and TNF-α, and BMDMs from ST2-/- showed reduced levels of these cytokines after stimulus with MSU crystals. CONCLUSION: IL-33 mediates gout pain and inflammation by boosting macrophages production of cytokines upon MSU crystals stimulus.