CCR9+CD4+ T cells are associated with disease activity in patients with rheumatoid arthritis.

An increase in CD4+ T cells in the synovium is closely linked to the pathogenesis of rheumatoid arthritis (RA). We aimed to identify the possible causes of the elevated CD4+ T cell levels and to explore the factors influencing disease activity in RA. Fifty-five RA patients, including 28 with active RA (ARA), 27 with inactive RA, and 22 healthy controls, were recruited for this study. The proportion of CCR9+CD4+ T cells and the expression of chemokine receptor 9 (CCR9) on CD4+ T cells were analyzed by flow cytometry. Enzyme-linked immunosorbent assay and chemiluminescent immunoassay were used to evaluate interleukin (IL)-17A and IL-6 levels, respectively. The proportion of CCR9+CD4+ T cells and the expression of CCR9 on CD4+ T cells increased significantly in peripheral blood (PB) and synovial fluid (SF) in ARA compared to those in inactive RA. Furthermore, SF contained more CCR9+CD4+ T cells, IL-6, and IL-17A than PB in RA patients. Moreover, CD4+ T cells in the PB of patients with RA, especially ARA, expressed more CCR9 and secreted more IL-6 and IL-17A after activation. Here, we also demonstrated that both the percentage of CCR9+ cells in CD4+ T cells and the expression of CCR9 on circulating CD4+ T cells were positively correlated with erythrocyte sedimentation rate, hypersensitive C-reactive protein, rheumatoid factor, and anti-cyclic citrullinated peptide antibody. CCR9+CD4+ T cells are elevated in PB and SF, and are associated with disease activity in patients with RA.

The Role of Semaphorins in the Pathogenesis of Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is one of the most common autoimmune diseases. Inflammation of the synovial fluid propagates the pathological process of angiogenesis. Semaphorins play a crucial role in the context of endothelial cell function, and their pleiotropic nature has various effects on the further development of RA. This narrative review summarises the various roles of semaphorins in the pathology of RA and whether they could play a role in developing novel RA treatment options.

Fibroblast expression of neurotransmitter receptor HTR2A associates with inflammation in rheumatoid arthritis joint.

The study of neuroimmune crosstalk and the involvement of neurotransmitters in inflammation and bone health has illustrated their significance in joint-related conditions. One important mode of cell-to-cell communication in the synovial fluid (SF) is through extracellular vesicles (EVs) carrying microRNAs (miRNAs). The role of neurotransmitter receptors in the pathogenesis of inflammatory joint diseases, and whether there are specific miRNAs regulating differentially expressed HTR2A, contributing to the inflammatory processes and bone metabolism is unclear. Expression of neurotransmitter receptors and their correlated inflammatory molecules were identified in rheumatoid arthritis (RA) and osteoarthritis (OA) synovium from a scRNA-seq dataset. Immunohistochemistry staining of synovial tissue (ST) from RA and OA patients was performed for validation. Expression of miRNAs targeting HTR2A carried by SF EVs was screened in low- and high-grade inflammation RA from a public dataset and validated by qPCR. HTR2A reduction by target miRNAs was verified by miRNAs mimics transfection into RA fibroblasts. HTR2A was found to be highly expressed in fibroblasts derived from RA synovial tissue. Its expression showed a positive correlation with the degree of inflammation observed. 5 miRNAs targeting HTR2A were decreased in RA SF EVs compared to OA, three of which, miR-214-3p, miR-3120-5p and miR-615-3p, mainly derived from monocytes in the SF, were validated as regulators of HTR2A expression. The findings suggest that fibroblast HTR2A may play a contributory role in inflammation and the pathogenesis of RA. Additionally, targeting miRNAs that act upon HTR2A could present novel therapeutic strategies for alleviating inflammation in RA.

The alterations in nerve growth factor concentration in plasma and synovial fluid before and after total knee arthroplasty.

Total knee arthroplasty (TKA) is an effective procedure for pain relief; however, the emergence of postsurgical pain remains a concern. In this study, we investigated the production of nerve growth factor (NGF) and mediators that affect NGF production and their function in the synovial fluid and plasma after TKA. This study included 19 patients (20 knees) who had rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and knee osteoarthritis (OA) who underwent TKA, categorized into OA and non-OA groups. The levels of NGF, inflammatory cytokines, and lipid mediators were analyzed before and after surgery. The intraoperative synovial fluid NGF concentration was more than seven times higher in the non-OA group than in the OA group. The intra-articular NGF levels increased significantly by more than threefold postoperatively in the OA group but not in the non-OA group. Moreover, the levels of inflammatory cytokines and lipid mediators were increased in the synovial fluid of both groups. The intra-articular cytokines or NGF concentrations positively correlated with postoperative pain. Targeted NGF control has the potential to alleviate postsurgical pain in TKA, especially in patients with OA, emphasizing the importance of understanding NGF dynamics under different knee conditions.

An update on the study of synovial fluid in the geriatric patient.

BACKGROUND: The characteristics of synovial fluid (SF) in geriatric patients differ from those in younger patients. In Mexico, epidemiologic data on the incidence of different rheumatic diseases in geriatric patients are scarce. OBJECTIVE: To describe the physical characteristics of geriatric SF and the prevalence of crystals in knee and other joint aspirates from patients with previously diagnosed joint disease. MATERIALS AND METHODS: A retrospective study was performed with a baseline of 517 SF samples between 2011 and 2023. White blood cell count was performed by Neubauer chamber and crystals were identified by polarized light microscopy. Descriptive statistical analysis was performed and prevalence was reported as a percentage. RESULTS: The mean age of the adults was 73.5±5.0 years, 54.4% were women and 45.6% were men. The mean SF volume was 6.3±9.5mL in older adults and 15.3±24.9mL in those younger than 65 years. The mean viscosity in older adults was 9.5±4.5mm and the mean leukocyte count was 7352±16,402leukocytes/mm3. Seventy percent of the older adults' SFs were referred to the laboratory for osteoarthritis (OA), with lower proportions for rheumatoid arthritis (RA) (14.6%) and gout (5.1%). Of the crystals observed in the geriatric population, 14.6% corresponded to monosodium urate crystals (CUM) and 18.9% to calcium pyrophosphate crystals (CPP). CONCLUSIONS: The characteristics of LS in older adults were smaller volume, increased viscosity, and non-inflammatory. The main diagnoses were OA, RA, and gout. The crystal content of the SF of the geriatric population corresponded mainly to CPP.

Efecto de la resección de la grasa del paquete infrapatelar de la rodilla en el desarrollo de la artrosis. Estudio experimental en ovejas / Infrapatellar Fat Pad resection effect on the osteoarthritis development: Experimental study in sheep

Introducción: La grasa de las articulaciones sinoviales puede servir para el mantenimiento de la estructura articular. Nuestro objetivo es analizar la evolución de la degeneración articular en rodillas con y sin paquete adiposo. Material y metodología: En 6 ovejas se efectuó la sección del ligamento cruzado anterior en ambas rodillas, para provocar una artrosis. En un grupo se preservó el paquete adiposo y en otro grupo se extirpó completamente. Realizamos un estudio histológico y de biología molecular analizando la expresión, en la membrana sinovial, el hueso subcondral, cartílago, grasa, menisco y líquido sinovial, de RUNX2, PTHrP, catepsina-K y MCP1. Resultados: No encontramos diferencias morfológicas. Encontramos aumento de la expresión de RUNX2 en membrana sinovial, PTHrP y Catepsina K en líquido sinovial en el grupo sin grasa y aumento de la expresión RUNX2 en el menisco y MCP1 en líquido sinovial en el grupo con grasa. Conclusión: La grasa infrapatelar participa en el proceso inflamatorio que acompaña en la artrosis, pues la resección de la grasa de Hoffa altera los marcadores proinflamatorios, mientras que el modelo con la grasa intacta incrementa el marcador proinflamatorio MCP1 en líquido sinovial.(AU)

Introduction: The fat of the synovial joints can be used to maintain the joint structure. Our objective is to analyze the evolution of joint degeneration in knees with and without adipose pack. Material and methodology: In six sheep, the anterior cruciate ligament was sectioned in both knees, to cause osteoarthritis. In one group the fat pack was preserved and in another group it was completely removed. We performed a histological and molecular biology study analyzing the expression, in the synovial membrane, subchondral bone, cartilage, fat, meniscus, and synovial fluid, of RUNX2, PTHrP, cathepsin-K, and MCP1. Results: We did not find morphological differences. We found increased expression of RUNX2 in synovial membrane, PTHrP and Cathepsin K in synovial fluid in the group without fat, and increased expression of RUNX2 in the meniscus and MCP1 in synovial fluid in the group with fat. Conclusion: Infrapatellar fat participates in the inflammatory process that accompanies osteoarthritis, since Hoffa fat pad resection alters pro-inflammatory markers, while the model with intact fat increases the pro-inflammatory marker MCP1 in synovial fluid.(AU)

[Translated article] Infrapatellar fat pad resection effect on the osteoarthritis development: Experimental study in sheep / Efecto de la resección de la grasa del paquete infrapatelar de la rodilla en el desarrollo de la artrosis. Estudio experimental en ovejas

Introducción: La grasa de las articulaciones sinoviales puede servir para el mantenimiento de la estructura articular. Nuestro objetivo es analizar la evolución de la degeneración articular en rodillas con y sin paquete adiposo. Material y metodología: En 6 ovejas se efectuó la sección del ligamento cruzado anterior en ambas rodillas, para provocar una artrosis. En un grupo se preservó el paquete adiposo y en otro grupo se extirpó completamente. Realizamos un estudio histológico y de biología molecular analizando la expresión, en la membrana sinovial, el hueso subcondral, cartílago, grasa, menisco y líquido sinovial, de RUNX2, PTHrP, catepsina-K y MCP1. Resultados: No encontramos diferencias morfológicas. Encontramos aumento de la expresión de RUNX2 en membrana sinovial, PTHrP y Catepsina K en líquido sinovial en el grupo sin grasa y aumento de la expresión RUNX2 en el menisco y MCP1 en líquido sinovial en el grupo con grasa. Conclusión: La grasa infrapatelar participa en el proceso inflamatorio que acompaña en la artrosis, pues la resección de la grasa de Hoffa altera los marcadores proinflamatorios, mientras que el modelo con la grasa intacta incrementa el marcador proinflamatorio MCP1 en líquido sinovial.(AU)

Introduction: The fat of the synovial joints can be used to maintain the joint structure. Our objective is to analyze the evolution of joint degeneration in knees with and without adipose pack. Material and methodology: In six sheep, the anterior cruciate ligament was sectioned in both knees, to cause osteoarthritis. In one group the fat pack was preserved and in another group it was completely removed. We performed a histological and molecular biology study analyzing the expression, in the synovial membrane, subchondral bone, cartilage, fat, meniscus, and synovial fluid, of RUNX2, PTHrP, cathepsin-K, and MCP1. Results: We did not find morphological differences. We found increased expression of RUNX2 in synovial membrane, PTHrP and Cathepsin K in synovial fluid in the group without fat, and increased expression of RUNX2 in the meniscus and MCP1 in synovial fluid in the group with fat. Conclusion: Infrapatellar fat participates in the inflammatory process that accompanies osteoarthritis, since Hoffa fat pad resection alters pro-inflammatory markers, while the model with intact fat increases the pro-inflammatory marker MCP1 in synovial fluid.(AU)

An update on the study of synovial fluid in the geriatric patient / Panorama actual del estudio de líquido sinovial en el paciente geriátrico

Background: The characteristics of synovial fluid (SF) in geriatric patients differ from those in younger patients. In Mexico, epidemiologic data on the incidence of different rheumatic diseases in geriatric patients are scarce. Objective: To describe the physical characteristics of geriatric SF and the prevalence of crystals in knee and other joint aspirates from patients with previously diagnosed joint disease. Materials and methods: A retrospective study was performed with a baseline of 517 SF samples between 2011 and 2023. White blood cell count was performed by Neubauer chamber and crystals were identified by polarized light microscopy. Descriptive statistical analysis was performed and prevalence was reported as a percentage. Results: The mean age of the adults was 73.5±5.0 years, 54.4% were women and 45.6% were men. The mean SF volume was 6.3±9.5mL in older adults and 15.3±24.9mL in those younger than 65 years. The mean viscosity in older adults was 9.5±4.5mm and the mean leukocyte count was 7352±16,402leukocytes/mm3. Seventy percent of the older adults’ SFs were referred to the laboratory for osteoarthritis (OA), with lower proportions for rheumatoid arthritis (RA) (14.6%) and gout (5.1%). Of the crystals observed in the geriatric population, 14.6% corresponded to monosodium urate crystals (CUM) and 18.9% to calcium pyrophosphate crystals (CPP). Conclusions: The characteristics of LS in older adults were smaller volume, increased viscosity, and non-inflammatory. The main diagnoses were OA, RA, and gout. The crystal content of the SF of the geriatric population corresponded mainly to CPP.(AU)

Antecedentes: Las características del líquido sinovial (LS) en pacientes geriátricos varían en comparación con pacientes más jóvenes. En México, los datos epidemiológicos sobre la incidencia de diversas enfermedades reumáticas en el paciente geriátrico son escasos. Objetivo: Describir las características físicas del LS geriátrico y la prevalencia de cristales en aspirados de rodilla y otras articulaciones de pacientes con enfermedades articulares previamente diagnosticadas.Materiales y métodos: Se realizó un estudio retrospectivo con una base de 517 muestras de LS entre 2011 y 2023. El recuento de glóbulos blancos se realizó con cámara de Neubauer, y los cristales se identificaron por microscopia de luz polarizada. Se realizó un análisis estadístico descriptivo y la prevalencia se reportó como porcentaje. Resultados: La edad promedio en los adultos fue de 73,5±5,0 años; el 54,4% fueron mujeres y el 45,6%, hombres. El volumen promedio del LS en adultos mayores fue de 6,3±9,5ml, mientras que en menores de 65 años fue de 15,3±24,9ml. La viscosidad promedio fue de 9,5±4,5mm en los adultos mayores, y una cuenta de 7.352±16.402 leucocitos/mm3. El 70% de los LS de los adultos mayores fueron remitidos a laboratorio por osteoartritis (OA), u una proporción más baja, por artritis reumatoide (AR) (14,6%) y gota (5,1%). En cuanto a los cristales observados en los LS de la población geriátrica, el 14,6% correspondieron a cristales de urato monosódico (CUM) y el 18,9%, a cristales de pirofosfato de calcio (CPP). Conclusiones: Las características del LS en los adultos mayores fueron menor volumen, viscosidad incrementada y no inflamatorios. Los principales diagnósticos fueron OA, AR y gota. El contenido de los cristales en los LS de la población geriátrica correspondió principalmente a CPP.(AU)

Performance of adenosine deaminase in synovial fluid for the diagnosis of tuberculous arthritis: A systematic review and meta-analysis.

OBJECTIVES: Adenosine deaminase (ADA) activity has shown good performance in diagnosing pleural, peritoneal, and meningeal tuberculosis. This meta-analysis aimed to evaluate the performance of measuring ADA activity in synovial fluid for the early diagnosis of joint tuberculosis. METHODS: We searched published information in MEDLINE, Embase, Cochrane Library, Web of Science, and MedRxiv databases, as well as unpublished information in the American College of Rheumatology and European League Against Rheumatism for conference abstracts (2012-2021). We also scanned the reference lists of articles. Two reviewers independently applied the criteria for selection, assessed quality, and extracted data (PROSPERO number CRD42021284472). RESULTS: Seven independent studies (N=305 subjects) that compared ADA activity in synovial fluid with a composite reference diagnostic method for tuberculosis were included. Overall, the risk of bias was judged low. Studies were classified as high quality (n=3; 148 subjects) and low quality (n=4; 157 subjects). Pooled sensitivity and specificity of ADA activity was 94% (95% confidence interval [CI], 0.89-98; I2=23%) and 88% (95% CI, 83-92; I2=83%), respectively. The random-effects model for pooled diagnostic Odds ratio was 67.1 (95%CI, 20.3-222.2; I2=30%). The receiver operating characteristic curve area was 0.96 (95% CI, 0.92-0.99). Meta-regression did not identify the quality of the study, country of publication, or the type of assay as a source of heterogeneity. CONCLUSIONS: Measuring ADA activity in synovial fluid demonstrates good performance for the early diagnosis of joint tuberculosis.

Endoplasmic reticulum stress-related protein GRP78 and CHOP levels in synovial fluid correlate with disease progression of primary knee osteoarthritis: A cross-sectional study.

BACKGROUND: Endoplasmic reticulum (ER) stress has been shown to play an important role in osteoarthritis (OA). OBJECTIVE: This study was aimed at assessing the relationship of endoplasmic reticulum (ER) stress-related glucose-regulated protein 78 (GRP78) and CCAAT/enhancer-binding protein homologous protein (CHOP) concentrations in the serum/synovial fluid (SF) with disease severity of primary knee osteoarthritis (pkOA). METHODS: Patients with pkOA together with healthy individuals were consecutively recruited from our hospital. The levels of GRP78 and CHOP in serum / SF were detected using enzyme-linked immunosorbent assay. The levels of IL-6 and MMP-3 were also examined. Radiographic progression of pkOA was evaluated based on Kellgren-Lawrence (K-L) grades. Receiver Operating Characteristic (ROC) curves were used to assess the diagnostic value of GRP78/CHOP levels with regard to K-L grades. The assessment of clinical severity was conducted using the visual analogue scale (VAS), Oxford knee score (OKS), and Lequesne algofunctional index (LAI). RESULTS: A total of 140 pkOA patients and 140 healthy individuals were included. Serum GRP78 and CHOP levels in pkOA patients were not significantly different from those in healthy individuals. The SF GRP78 and CHOP levels in healthy controls were not detected due to ethical reasons. Compared to those with K-L grade 2 and 3, the pkOA patients with K-L grade 4 had higher GRP78 and CHOP levels in the SF with statistical significance. In addition, the pkOA patients with K-L grade 3 exhibited drastically upregulated GRP78 and CHOP concentrations in the SF compared to those with K-L grade 2. Positive correlations of GRP78 and CHOP levels with K-L grades, IL-6, and MMP-3 levels in the SF were observed. ROC curve analysis indicated that both GRP78 and CHOP levels may act as decent indicators with regard to OA. GRP78 and CHOP concentrations in the SF were positively correlated with VAS/LAI score and negatively associated with OKS score. CONCLUSION: The study indicated that GRP78 and CHOP levels in the SF but not the serum were positively correlated with disease severity of pkOA.

Inhibition of complement C3 prevents osteoarthritis progression in guinea pigs by blocking STAT1 activation.

Osteoarthritis (OA) is one of the leading causes of disability, affecting over 500 million adults worldwide. Previous studies have found that various inflammatory factors can contribute to the pathogenesis of OA, including complement factors in the synovial fluid of OA patients. However, the pathogenesis of this disease is still not known, and the only therapy of severe OA is total joint replacements. Total joint replacements are invasive, expensive, and affect quality of life. Here we show that when human articular chondrocytes are stimulated with pro-inflammatory mediator interleukin-1ß (IL-1ß) there is an increase in inflammatory factors including complement component 3 (C3). We also found the transcription factor, signal transducer and activator of transcription 1 (STAT1), is responsible for increased C3 expression after IL-1ß stimulation in human articular chondrocytes. A specific STAT1 inhibitor, fludarabine, attenuates the hyper-expression of C3 and delays/prevents spontaneous OA in Dunkin-Hartley guinea pigs. Since fludarabine is already clinically used for chemotherapy, this study has great translational potential as a unique disease-modifying osteoarthritis drug (DMOAD) in treating primary OA.

Metabolic profiling of synovial fluid in human temporomandibular joint osteoarthritis.

Introduction: Temporomandibular joint (TMJ) osteoarthritis (OA) is a common TMJ degenerative disease with an unclear mechanism. Synovial fluid (SF), an important component of TMJ, contains various proteins and metabolites that may directly contribute to OA. The present study aimed to investigate the influence of SF in TMJOA at the metabolite level. Methods: Untargeted and widely targeted metabolic profiling were employed to identify metabolic changes in SF of 90 patients with different TMJOA grades according to TMJ magnetic resonance imaging. Results: A total 1498 metabolites were detected. Most of the metabolites were amino acids and associated metabolites, benzene and substituted derivatives, and lipids. Among patients with mild, moderate and severe TMJOA, 164 gradually increasing and 176 gradually decreasing metabolites were identified, indicating that biosynthesis of cofactors, choline metabolism, mineral absorption and selenocompound metabolism are closely related to TMJOA grade. Combined metabolomics and clinical examination revealed 37 upregulated metabolites and 16 downregulated metabolites in patients with pain, of which 19 and 26 metabolites were positively and negatively correlated, respectively, with maximum interincisal opening. A model was constructed to diagnose TMJOA grade and nine biomarkers were identified. The identified metabolites are key to exploring the mechanism of TMJOA. Discussion: In the present study, a metabolic profile was constructed and assessed using a much larger number of human SF samples from patients with TMJOA, and a model was established to contribute to the diagnosis of TMJOA grade. The findings expand our knowledge of metabolites in human SF of TMJOA patients, and provide an important basis for further research on the pathogenesis and treatment of TMJOA.

Antibodies to Borrelia burgdorferi and Bartonella species in serum and synovial fluid from people with rheumatic diseases.

Vector-borne infections may underlie some rheumatic diseases, particularly in people with joint effusions. This study aimed to compare serum and synovial fluid antibodies to B. burgdorferi and Bartonella spp. in patients with rheumatic diseases. This observational, cross-sectional study examined paired synovial fluid and serum specimens collected from 110 patients with joint effusion between October 2017 and January 2022. Testing for antibodies to B. burgdorferi (using CDC criteria) and Bartonella spp. via two indirect fluorescent antibody (IFA) assays was performed as part of routine patient care at the Institute for Specialized Medicine (San Diego, CA, USA). There were 30 participants (27%) with positive two-tier B. burgdorferi serology and 26 participants (24%) with IFA seroreactivity (≥1:256) to B. henselae and/or B. quintana. Both B. burgdorferi IgM and IgG were detected more frequently in synovial fluid than serum: 27% of patients were either IgM or IgG positive in synovial fluid, compared to 15.5% in serum (P = 0.048). Conversely, B. henselae and B. quintana antibodies were detected more frequently in serum than synovial fluid; overall only 2% of patients had positive IFA titers in synovial fluid, compared to 24% who had positive IFA titers in serum (P < 0.001). There were no significant associations between B. burgdorferi or Bartonella spp. seroreactivity with any of the clinical rheumatological diagnoses. This study provides preliminary support for the importance of synovial fluid antibody testing for documenting exposure to B. burgdorferi but not for documenting exposure to Bartonella spp. IMPORTANCE: This study focuses on diagnostic testing for two common vector-borne diseases in an affected patient population. In it, we provide data showing that antibodies to B. burgdorferi, but not Bartonella spp., are more commonly found in synovial fluid than serum of patients with joint effusion. Since Lyme arthritis is a common-and sometimes difficult to diagnose-rheumatic disease, improving diagnostic capabilities is of utmost importance. While our findings are certainly not definitive for changes to practice, they do suggest that synovial fluid could be a useful sample for the clinical diagnosis of Lyme disease, and future prospective studies evaluating this claim are warranted.

Peptidoglycan in osteoarthritis synovial tissue is associated with joint inflammation.

OBJECTIVES: Peptidoglycan (PG) is an arthritogenic bacterial cell wall component whose role in human osteoarthritis is poorly understood. The purpose of this study was to determine if PG is present in synovial tissue of osteoarthritis patients at the time of primary total knee arthroplasty (TKA), and if its presence is associated with inflammation and patient reported outcomes. METHODS: Intraoperative synovial tissue and synovial fluid samples were obtained from 56 patients undergoing primary TKA, none of whom had history of infection. PG in synovial tissue was detected by immunohistochemistry (IHC) and immunofluorescence microscopy (IFM). Synovial tissue inflammation and fibrosis were assessed by histopathology and synovial fluid cytokine quantification. Primary human fibroblasts isolated from arthritis synovial tissue were stimulated with PG to determine inflammatory cytokine response. RESULTS: A total of 33/56 (59%) of primary TKA synovial tissue samples were positive for PG by IHC, and PG staining colocalized with markers of synovial macrophages and fibroblasts by IFM. Synovial tissue inflammation and elevated IL-6 in synovial fluid positively correlated with PG positivity. Primary human fibroblasts stimulated with PG secreted high levels of IL-6, consistent with ex vivo findings. Interestingly, we observed a significant inverse correlation between PG and age at time of TKA, indicating younger age at time of TKA was associated with higher PG levels. CONCLUSION: Peptidoglycan is commonly found in synovial tissue from patients undergoing TKA. Our data indicate that PG may play an important role in inflammatory synovitis, particularly in patients who undergo TKA at a relatively younger age.

Enzymatic digestion does not compromise sliding-mediated cartilage lubrication.

Articular cartilage's remarkable low-friction properties are essential to joint function. In osteoarthritis (OA), cartilage degeneration (e.g., proteoglycan loss and collagen damage) decreases tissue modulus and increases permeability. Although these changes impair lubrication in fully depressurized and slowly slid cartilage, new evidence suggests such relationships may not hold under biofidelic sliding conditions more representative of those encountered in vivo. Our recent studies using the convergent stationary contact area (cSCA) configuration demonstrate that articulation (i.e., sliding) generates interfacial hydrodynamic pressures capable of replenishing cartilage interstitial fluid/pressure lost to compressive loading through a mechanism termed tribological rehydration. This fluid recovery sustains in vivo-like kinetic friction coefficients (µk<0.02 in PBS and <0.005 in synovial fluid) with little sensitivity to mechanical properties in healthy tissue. However, the tribomechanical function of compromised cartilage under biofidelic sliding conditions remains unknown. Here, we investigated the effects of OA-like changes in cartilage mechanical properties, modeled via enzymatic digestion of mature bovine cartilage, on its tribomechanical function during cSCA sliding. We found no differences in sliding-driven tribological rehydration behaviors or µk between naïve and digested cSCA cartilage (in PBS or synovial fluid). This suggests that OA-like cartilage retains sufficient functional properties to support naïve-like fluid recovery and lubrication under biofidelic sliding conditions. However, OA-like cartilage accumulated greater total tissue strains due to elevated strain accrual during initial load application. Together, these results suggest that elevated total tissue strains-as opposed to activity-mediated strains or friction-driven wear-might be the key biomechanical mediator of OA pathology in cartilage. STATEMENT OF SIGNIFICANCE: Osteoarthritis (OA) decreases cartilage's modulus and increases its permeability. While these changes compromise frictional performance in benchtop testing under low fluid load support (FLS) conditions, whether such observations hold under sliding conditions that better represent the joints' dynamic FLS conditions in vivo is unclear. Here, we leveraged biofidelic benchtop sliding experiments-that is, those mimicking joints' native sliding environment-to examine how OA-like changes in mechanical properties effect cartilage's natural lubrication. We found no differences in sliding-mediated fluid recovery or kinetic friction behaviors between naïve and OA-like cartilage. However, OA-like cartilage experienced greater strain accumulation during load application, suggesting that elevated tissue strains (not friction-driven wear) may be the primary biomechanical mediator of OA pathology.

Alterations in articular cartilage frictional properties in the setting of acute gouty arthritis.

The tribological behaviour of articular cartilage plays a key role in joint motion; however, there is a gap in research on the effect of hyperuricemic joint fluid on cartilage friction behaviour in acute gouty arthritis. In this study, we carried out a fixed-load scratch experiment to compare the friction and wear of articular cartilage under the lubrication of gouty arthritis arthritic fluid and normal human arthritic fluid, and the results showed that the cartilage friction coefficient of patients with acute gouty arthritis was significantly larger than that of normal human beings, and that the cartilage friction coefficient decreased with the elevation of normal load and sliding speed, and the change with the sliding speed varied more differently from that of normal human beings, and that the cartilage surface wear was more severe after prolonged friction. The wear and tear of the cartilage surface is more severe after prolonged friction. Patients with gouty arthritis should reduce the sudden speed changes such as fast running and variable speed running to maintain the stability of the cartilage surface friction coefficient.

Performance of adenosine deaminase in synovial fluid for the diagnosis of tuberculous arthritis: A systematic review and meta-analysis / Rendimiento de la adenosina desaminasa en el líquido sinovial para el diagnóstico de la artritis tuberculosa: una revisión sistemática y metaanálisis

Objectives: Adenosine deaminase (ADA) activity has shown good performance in diagnosing pleural, peritoneal, and meningeal tuberculosis. This meta-analysis aimed to evaluate the performance of measuring ADA activity in synovial fluid for the early diagnosis of joint tuberculosis. Methods: We searched published information in MEDLINE, Embase, Cochrane Library, Web of Science, and MedRxiv databases, as well as unpublished information in the American College of Rheumatology and European League Against Rheumatism for conference abstracts (2012–2021). We also scanned the reference lists of articles. Two reviewers independently applied the criteria for selection, assessed quality, and extracted data (PROSPERO number CRD42021284472). Results: Seven independent studies (N=305 subjects) that compared ADA activity in synovial fluid with a composite reference diagnostic method for tuberculosis were included. Overall, the risk of bias was judged low. Studies were classified as high quality (n=3; 148 subjects) and low quality (n=4; 157 subjects). Pooled sensitivity and specificity of ADA activity was 94% (95% confidence interval [CI], 0.89–98; I2=23%) and 88% (95% CI, 83–92; I2=83%), respectively. The random-effects model for pooled diagnostic Odds ratio was 67.1 (95%CI, 20.3–222.2; I2=30%). The receiver operating characteristic curve area was 0.96 (95% CI, 0.92–0.99). Meta-regression did not identify the quality of the study, country of publication, or the type of assay as a source of heterogeneity. Conclusions: Measuring ADA activity in synovial fluid demonstrates good performance for the early diagnosis of joint tuberculosis.(AU)

Objetivos: La actividad de la adenosina desaminasa (ADA) ha mostrado un buen desempeño en el diagnóstico de la tuberculosis pleural, peritoneal y meníngea. Este metaanálisis tuvo como objetivo evaluar el rendimiento de la medición de la actividad de la ADA en el líquido sinovial para el diagnóstico precoz de la tuberculosis articular. Métodos: Se realizaron búsquedas de resúmenes de congresos en la información publicada en las bases de datos MEDLINE, Embase, Cochrane Library, Web of Science y MedRxiv, así como en información no publicada en el American College of Rheumatology y la European League Against Rheumatism (2012-2021). También se escanearon las listas de referencias de los artículos. Dos revisores aplicaron de forma independiente los criterios de selección, evaluaron la calidad y extrajeron los datos (número PROSPERO CRD42021284472). Resultados: Se incluyeron siete estudios independientes (n=305 sujetos) que compararon la actividad de la ADA en el líquido sinovial con un método diagnóstico compuesto de referencia para la tuberculosis. En general, el riesgo de sesgo se consideró bajo. Los estudios se clasificaron como de alta calidad (n=3; 148 sujetos) y de baja calidad (n=4; 157 sujetos). La sensibilidad y la especificidad agrupadas de la actividad de la ADA fueron del 94% (intervalo de confianza [IC] del 95%: 0,89-98; I2=23%) y del 88% (IC95%: 83-92; I2=83%), respectivamente. El modelo de efectos aleatorios para el odds ratio diagnóstico agrupado fue de 67,1 (IC95%: 20,3-222,2; I2=30%). El área de la curva característica de operación del receptor fue de 0,96 (IC95%: 0,92-0,99). La metarregresión no identificó la calidad del estudio, el país de publicación o el tipo de ensayo como fuente de heterogeneidad.Conclusiones: La medición de la actividad de ADA en el líquido sinovial demuestra un buen rendimiento para el diagnóstico precoz de la tuberculosis articular.(AU)

Single-cell profiling identifies IL1Bhi macrophages associated with inflammation in PD-1 inhibitor-induced inflammatory arthritis.

Inflammatory arthritis (IA) is a common rheumatic adverse event following immune checkpoint inhibitors treatment. The clinical disparities between IA and rheumatoid arthritis (RA) imply disease heterogeneity and distinct mechanisms, which remain elusive. Here, we profile CD45+ cells from the peripheral blood or synovial fluid (SF) of patients with PD-1-induced IA (PD-1-IA) or RA using single-cell RNA sequencing. We report the predominant expansion of IL1Bhi myeloid cells with enhanced NLRP3 inflammasome activity, in both the SF and peripheral blood of PD-1-IA, but not RA. IL1Bhi macrophages in the SF of PD-1-IA shared similar inflammatory signatures and might originate from peripheral IL1Bhi monocytes. Exhausted CD8+ T cells (Texs) significantly accumulated in the SF of patients with PD-1-IA. IL1Bhi myeloid cells communicated with CD8+ Texs possibly via the CCR1-CCL5/CCL3 and CXCL10-CXCR3 axes. Collectively, these results demonstrate different cellular and molecular pathways in PD-1-IA and RA and highlight IL1Bhi macrophages as a possible therapeutic target in PD-1-IA.

Comparative study of clinical and MRI features of TMD patients with or without joint effusion: a retrospective study.

BACKGROUND: The relationship between joint effusion and temporomandibular disorders (TMD) remains unclear. The purpose of this study was to investigate the correlation among joint effusion, clinical features and MRI imaging features of TMD. METHODS: A total of 1532 temporomandibular joints (TMJs) from 766 patients (605 females and 161 males) with the mean age of 31.68 ± 13.71 years from January 2022 to June 2023 were included in the study. Clinical and MRI features were collected and analyzed. Chi-Square test, Spearman correlation coefficient and binary logistic regression analysis were performed. RESULTS: Patients with joint effusion were significantly older and had smaller value of MIO (p < 0.001). There were significant differences in the distribution of joint sounds (with or without), joint pain (with or without), disc morphology (biconcave, contracture, irregular and lengthened) and disc position between joint effusion group (JE) and non-joint effusion group (NA) (P < 0.05).The odds of having joint effusion were 1.726 higher in patients with joint sounds when compared to those without joint sounds. The odds of having joint effusion were 8.463 higher in patients with joint pain when compared to those without joint pain. The odds of having joint effusion were 2.277 higher in patients with contracture when compared to those with biconcave. The odds of having joint effusion were 1.740 higher in patients with anterior disc displacement with reduction (ADDWR) when compared to those with normal disc position. The prediction accuracy of this model is 74.9%, and the area under curve (AUC) is 79.5%, indicating that it can be used for the prediction and the judgment effect is average. CONCLUSIONS: The results demonstrated that joint sounds, joint pain, contracture, and ADDWR are high risk factors for joint effusion, especially joint pain. TRIAL REGISTRATION: This study was retrospectively registered on 28/03/2022 and endorsed by the Ethics Committee of Affiliated Stomatology Hospital of Guangzhou Medical University (LCYJ2022014).

Does Chronic Pancreatitis in Growing Pigs Lead to Articular Cartilage Degradation and Alterations in Subchondral Bone?

Chronic pancreatitis (CP), a progressive inflammatory disease, poses diagnostic challenges due to its initially asymptomatic nature. While CP's impact on exocrine and endocrine functions is well-recognized, its potential influence on other body systems, particularly in young individuals, remains underexplored. This study investigates the hypothesis that CP in growing pigs leads to alterations in articular cartilage and subchondral bone, potentially contributing to osteoarthritis (OA) development. Utilizing a pig model of cerulein-induced CP, we examined the structural and compositional changes in subchondral bone, articular cartilage, and synovial fluid. Histological analyses, including Picrosirius Red and Safranin-O staining, were employed alongside immuno-histochemistry and Western blotting techniques. Our findings reveal significant changes in the subchondral bone, including reduced bone volume and alterations in collagen fiber composition. Articular cartilage in CP pigs exhibited decreased proteoglycan content and alterations in key proteins such as MMP-13 and TGF-ß1, indicative of early cartilage degradation. These changes suggest a link between CP and musculoskeletal alterations, underscoring the need for further research into CP's systemic effects. Our study provides foundational insights into the relationship between CP and skeletal health, potentially guiding future pediatric healthcare strategies for early CP diagnosis and management.