Differences in the Synovial Fluid Proteome of Septic and Aseptic Implant Failure.

Implant loosening is a severe complication after total joint replacement. Here, differential diagnosis between septic and aseptic cases is crucial for further surgical treatment, but low-grade periprosthetic joint infections (PJIs) in particular remain a challenge. In this study, we analyzed the synovial fluid proteome of 21 patients undergoing revision surgery for septic (eight cases) or aseptic (thirteen cases) implant failure using LC-MS/MS to identify potential new biomarkers as future diagnostic tools. Staphylococci were found in four cases, Streptococci in two cases, Serratia marcescens and Cutibacterium acnes in one case. Proteomic analysis of the synovial fluid resulted in the identification of 515 different proteins based on at least two peptides. A statistical comparison revealed 37 differentially abundant proteins (p < 0.05), of which 17 proteins (46%) showed a higher abundance in the septic group. The proteins with the highest fold change included the known marker proteins c-reactive protein (7.57-fold) and the calprotectin components protein S100-A8 (4.41-fold) and protein S100-A9 (3.1-fold). However, the protein with the highest fold change was leucine-rich alpha-2-glycoprotein 1 (LRG1) (9.07-fold), a currently discussed new biomarker for inflammatory diseases. Elevated LRG1 levels could facilitate the diagnosis of PJI in the future, but their significance needs to be further investigated.

Sex diferences in serum and synovial fluid C-reactive protein concentration in healthy dogs.

Differences between serum C-reactive protein (SCRP) and synovial fluid C-reactive protein (SFCRP) concentrations in healthy animals may be influenced by the sex of the individual and associated with various factors. The objective of this study was to evaluate the disparities in SCRP and SFCRP concentrations between females and males, as well as within each sex. Sixty healthy dogs (N = 60), comprising both sexes, were enrolled in the study. Peripheral blood and knee synovial fluid samples were collected for SCRP and SFCRP analysis, respectively. Serum C-reactive protein (SCRP) and SFCRP concentrations were measured, with mean of 9.61 ± 4.96 mg/L for SCRP and 1.28 ± 3.05 mg/L for SFCRP. Notably, SFCRP concentrations were consistently lower than SCRP concentrations in both sexes. Statistically significant differences were observed between sexes for both SCRP (P = 0.021) and SFCRP (P = 0.007). Further analysis within females revealed statistically significant differences between SCRP and SFCRP concentrations (P = 0.002), whereas in males, such differences were not significant (P = 0.175). Additionally, weak correlations were found between SCRP and SFCRP concentrations for both sexes (females r = 0.07; males r = 0.29). Joint capsule thickness was assessed using ultrasonography, revealing thicker joint capsules in males. A robust positive association was noted between joint capsule thickness and the SFCRP concentration in both sexes. These findings offer valuable insights into the dynamics of CRP in the context of joint health in male and female patients, elucidating the underlying pathological mechanisms of joint disease and inflammation. Overall, this underscores the importance of considering sex-specific factors in the assessment and management of joint health, as well as in the design and interpretation of studies involving SFCRP concentrations.

A Dual Functional Bioinspired Lubricant for Osteoarthritis Treatment and Potential Prevention.

Osteoarthritis (OA), primarily characterized by the deterioration of articular cartilage, is a highly prevalent joint-disabling disease. The pathological onset and progression of OA are closely related to cartilage lubrication dysfunction and synovial inflammation. Synergistic options targeted at restorative lubrication and anti-inflammation are expected to be the most attractive candidates to treat OA and perhaps help prevent it. Herein, a bioinspired lubricant (HA/PA@Lipo) was fabricated by combining anionic hyaluronan-graft-poly(2-acrylamide-2-methylpropanesulfonic acid sodium salt) (HA/PA) with cationic liposomes (Lipo) via electrostatic interaction. HA/PA@Lipo mimicked the lubrication complex located on the outer cartilage surface and was endowed cartilage with excellent cartilage-lubricating performances. After the antioxidant gallic acid (GA) was loaded for dual functionality, HA/PA@Lipo-GA was prepared with added anti-inflammatory properties. HA/PA@Lipo-GA showed favorable biocompatibility with C28/I2 cells, inhibited the production of reactive oxygen, and regulated the expression levels of anabolic genes and proteins. The therapeutic effects of HA/PA@Lipo-GA were evaluated using a sodium iodoacetate-induced OA rat model, and the preventive effects of HA/PA@Lipo-GA were estimated in vivo. The results suggested the robust potential of HA/PA@Lipo-GA with dual functions as a candidate option for OA treatment and prevention.

Infrared Spectroscopy of Synovial Fluid Shows Accuracy as an Early Biomarker in an Equine Model of Traumatic Osteoarthritis.

Osteoarthritis is a leading cause of lameness and joint disease in horses. A simple, economical, and accurate diagnostic test is required for routine screening for OA. This study aimed to evaluate infrared (IR)-based synovial fluid biomarker profiling to detect early changes associated with a traumatically induced model of equine carpal osteoarthritis (OA). Unilateral carpal OA was induced arthroscopically in 9 of 17 healthy thoroughbred fillies; the remainder served as Sham-operated controls. The median age of both groups was 2 years. Synovial fluid (SF) was obtained before surgical induction of OA (Day 0) and weekly until Day 63. IR absorbance spectra were acquired from dried SF films. Following spectral pre-processing, predictive models using random forests were used to differentiate OA, Sham, and Control samples. The accuracy for distinguishing between OA and any other joint group was 80%. The classification accuracy by sampling day was 87%. For paired classification tasks, the accuracies by joint were 75% for OA vs. OA Control and 70% for OA vs. Sham. The accuracy for separating horses by group (OA vs. Sham) was 68%. In conclusion, SF IR spectroscopy accurately discriminates traumatically induced OA joints from controls.

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.

The False-Positive Rate of Synovial Fluid Culture at a Single Clinical Laboratory Using Culture Bottles.

Introduction Synovial fluid (SF) cultures can yield false-positive or negative results when diagnosing periprosthetic joint infection (PJI). False-positives may arise during sample collection or from laboratory contamination. Understanding false-positive SF culture rates is crucial for interpreting PJI laboratory data, yet clinical laboratories rarely report these rates. This study aimed to define the false-positive SF culture rate at a major specialized clinical laboratory. Methods This study retrospectively analyzed prospectively collected data at a single clinical laboratory that receives SF for clinical testing for PJI. A total of 180,317 periprosthetic SF samples from the hip, knee, and shoulder were identified from January 2016 to December 2023, which met the inclusion criteria for this study. Samples were classified by both a modified 2018 International Consensus Meeting (ICM) score and an inflammation score that combined the SF-C-reactive protein, alpha-defensin, SF-white blood cell count, and SF-polymorphonuclear% into one standardized metric. Logistic regression was utilized to evaluate the impact of various collection-based characteristics on culture positivity, including inflammation biomarkers, the source joint, quality control metrics, and days of specimen transport to the laboratory. SF culture false-positivity was calculated based on the ICM category of "not-infected" or low inflammation score. Results Overall, 13.3% (23,974/180,317) of the samples were associated with a positive culture result: 12.5% for knee samples, 20.3% for hip samples, and 14.7% for shoulder samples. The false-positive SF culture rate among 131,949 samples classified as "not-infected" by the modified 2018 ICM definition was 0.47% (95%CI: 0.43 to 0.51%). Stratification by joint revealed a false-positive rate of 0.34% (95%CI: 0.31 to 0.38%) for knee samples, 1.24% (95%CI: 1.05 to 1.45%) for hip samples, and 3.02% (95%CI: 2.40 to 3.80%) for shoulder samples, with p < 0.0001 for all comparisons. The false-positive SF culture rate among 90,156 samples, representing half of all samples with the lowest standardized inflammation scores, was 0.47% (95%CI: 0.43 to 0.52%). Stratification by joint revealed a false-positive rate of 0.33% (95%CI: 0.29 to 0.37%) for knee samples, 1.45% (95%CI: 1.19 to 1.77%) for hip samples, and 3.09% (95%CI: 2.41 to 3.95%) for shoulder samples, with p<0.0001 for all comparisons. Multivariate logistic regression demonstrated the joint source (hip, shoulder) and poor sample quality as collection-based factors associated with a false-positive culture. Evaluation of a cohort of samples selected to minimize collection-based causes of false-positive culture demonstrated a false-positive rate of 0.30%, representing the ceiling limit for laboratory-based SF culture false-positivity. Conclusions This study utilizes two methods to estimate the false-positive SF culture rate at a single specialized clinical laboratory, demonstrating an overall false-positive rate of approximately 0.5%. Stratification of samples by source joint demonstrated that periprosthetic SF from the shoulder and hip have a substantially higher false-positive culture rate than that of the knee. The lowest false-positive SF culture rate (0.30%) was observed among samples from the knee-passing quality control. Culture positivity due to contamination at this specific laboratory is less than 0.30% because all specimens undergo identical processing.

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)

S100A12 is involved in the pathology of osteoarthritis by promoting M1 macrophage polarization via the NF-κB pathway.

BACKGROUND: Osteoarthritis (OA) is a degenerative joint disease that affects millions worldwide. Synovitis and macrophage polarization are important factors in the development of OA. However, the specific components of synovial fluid (SF) responsible for promoting macrophage polarization remain unclear. METHODS: Semi-quantitative antibody arrays were used to outline the proteome of SF. Differential expression analysis and GO/KEGG were performed on the obtained data. Immunohistochemistry and ELISA were used to investigate the relationship between SF S100A12 levels and synovitis levels in clinalclinical samples. In vitro cell experiments were conducted to investigate the effect of S100A12 on macrophage polarization. Public databases were utilized to predict and construct an S100A12-centered lncRNA-miRNA-mRNA competing endogenous RNA network, which was preliminarily validated using GEO datasets. RESULTS: The study outlines the protein profile in OA and non-OA SF. The results showed that the S100A12 level was significantly increased in OA SF and inflammatory chondrocytes. The OA synovium had more severe synovitis and higher levels of S100A12 than non-OA synovium. Exogenous S100A12 upregulated the levels of M1 markers and phosphorylated p65 and promoted p65 nuclear translocation, while pretreatment with BAY 11-7082 reversed these changes. It was also discovered that LINC00894 was upregulated in OA and significantly correlated with S100A12, potentially regulating S100A12 expression by acting as a miRNA sponge. CONCLUSIONS: This study demonstrated that S100A12 promotes M1 macrophage polarization through the NF-κB pathway, and found that LINC00894 has the potential to regulate the expression of S100A12 as a therapeutic approach.

Sex-specific effects of injury and beta-adrenergic activation on metabolic and inflammatory mediators in a murine model of post-traumatic osteoarthritis.

OBJECTIVE: Metabolic processes are intricately linked to the resolution of innate inflammation and tissue repair, two critical steps for treating post-traumatic osteoarthritis (PTOA). Based on lipolytic and immunoregulatory actions of norepinephrine, we hypothesized that intra-articular ß-adrenergic receptor (ßAR) stimulation would suppress PTOA-associated inflammation in the infrapatellar fat pad (IFP) and synovium. DESIGN: We used the ßAR agonist isoproterenol to perturb intra-articular metabolism 3.5 weeks after applying a non-invasive single-load compression injury to knees of 12-week-old male and female mice. We examined the acute effects of intra-articular isoproterenol treatment relative to saline on IFP histology, multiplex gene expression of synovium-IFP tissue, synovial fluid metabolomics, and mechanical allodynia. RESULTS: Injured knees developed PTOA pathology characterized by heterotopic ossification, articular cartilage loss, and IFP atrophy and fibrosis. Isoproterenol suppressed the upregulation of pro-fibrotic genes and downregulated the expression of adipose genes and pro-inflammatory genes (Adam17, Cd14, Icam1, Csf1r, and Casp1) in injured joints of female (but not male) mice. Analysis of published single-cell RNA-seq data identified elevated catecholamine-associated gene expression in resident-like synovial-IFP macrophages after injury. Injury substantially altered synovial fluid metabolites by increasing amino acids, peptides, sphingolipids, phospholipids, bile acids, and dicarboxylic acids, but these changes were not appreciably altered by isoproterenol. Intra-articular injection of either isoproterenol or saline increased mechanical allodynia in female mice, whereas neither substance affected male mice. CONCLUSIONS: Acute ßAR activation altered synovial-IFP transcription in a sex and injury-dependent manner, suggesting that women with PTOA may be more sensitive than men to treatments targeting sympathetic neural signaling pathways.

The Cytological Energy Detection of Purulent Inflammation in Synovial Fluid Is Not All Black and White.

Neutrophils are frequently found in the cytological picture of synovial fluid in several joint pathologies, and a higher proportion of them can even wrongly indicate these cases as purulent inflammation. For reliable differentiation between purulent and non-purulent cases, we use the cytological energy analysis of the synovial fluid. Using this method, we examined 350 knee joint synovial fluid samples. Overall, we found that the percentage of neutrophils ranged between 20.0% and 50.0% in 44 (12.6%) cases and was above 50.0% in 231 (66.0%) cases. In the same group, only 85 (24.3%) highly anaerobic synovial fluid samples were evaluated as purulent inflammation, and another 17 (4.9%) cases were evaluated as very likely purulent inflammation. Further, we quantified the immediate risk of purulent inflammation using the "purulent score" (PS). Of the total of 350 samples, 103 (29.4%) cases were classified as having a very high risk of purulent inflammation (PS = 4), 53 (15.1%) cases were classified as having a significant risk of purulent inflammation (PS = 3), 17 (4.9%) cases were classified as having a moderate risk of purulent inflammation (PS = 2), and 75 (21.4%) cases were classified as having no immediate risk of purulent inflammation (PS = 1). Based on our results and analyses, the cytological energy analysis of synovial fluid is an effective method that can be used to detect and specify joint inflammation and the risk of septic arthritis development.

Lactic Acid-Induced Colloidal Microrheology of Synovial Fluids.

The presence of colloidal scaffolds composed of proteins and hyaluronic acid engenders unique viscous and elastic properties to the synovial fluid (SF). While the elastic resistance of SF due to the presence of such nanoscale structures provides the load-bearing capacity, the viscous nature enables fluidity of the joints during the movements to minimize the wear and tear of the adjacent muscle, cartilage, or bone tissues. It is well-known that the hypoxic conditions at the bone joints often increase the lactic acid (LA) concentration due to the occurrence of excess anaerobic respiration during either hyperactivity or arthritic conditions. The present study uncovers that in such a scenario, beyond a critical loading of LA, the colloidal nanoscaffolds of SF break down to precipitate higher molecular weight (MW) proteins and hyaluronic acid (HA). Subsequently, the viscosity and elasticity of SF reduce drastically to manifest a fluid that has reduced load bearing and wear and tear resistance capacity. Interestingly, the study also suggests that a heathy SF is a viscoelastic fluid with a mild Hookean elasticity and non-Newtonian fluidity, which eventually transforms into a viscous watery liquid in the presence of a higher loading of LA. We employ this knowledge to biosynthesize an artificial SF that emulates the characteristics of the real one. Remarkably, the spatiotemporal microscopic images uncover that even for the artificial SF, a dynamic cross-linking of the high MW proteins and HA takes place before precipitating out of the same from the artificial SF matrix, emulating the real one. Control experiments suggest that this phenomenon is absent in the case when LA is mixed with either pure HA or proteins. The experiments unfold the specific role of LA in the destruction of colloidal nanoscaffolds of synovia, which is an extremely important requirement for the biosynthesis and translation of artificial synovial fluid.

Exploring the Mechanism of Acupuncture's Influence on the Protease Activity and Free Radical Damage in Synovial Fluid of Rheumatoid Arthritis Rats Induced by Type II Collagen from the Release of Active Oxygen.

Acupuncture was studied to investigate the mechanism of its effect on protease vitality and free radical damage in Type I CIA rats induced by type II collagen. The study divided rats into a control group (injected with physiological saline, n = 10), a model group (injected with type II collagen, n = 10), and an intervention group (injected with type II collagen + acupuncture ST36 and GB39, 3 times a week, for a total of 4 weeks, n = 10) based on the different injected drugs. Then, various indicators of the mice were experimentally tested using joint index scoring, H&E histological staining, protein blotting, and immunohistochemistry staining methods. Acupuncture ST36 and GB39 can reduce arthritis scores, histological staining scores, and increase MVD in CIA rats. And reduce protease levels, alleviate inflammation, synovial hyperplasia, and angiogenesis. In addition, the intervention group TNF-α, IL-1ß and IL-6 mRNA were reduced, and the clearance rates of hydrogen peroxide free radicals and nitric oxide free radicals were increased. The expression levels of ROS and MDA decrease, while the expression levels of SOD increase It has been proved that acupuncture at ST36 and GB39 can inhibit the release of ROS, reduce protease activity, inflammation, synovial hyperplasia, angiogenesis and free radical damage, thus reducing the severity of CIA (Collagen-Induced Arthritis) in rats.

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.

Quantitative MRI assessment of joint effusion using T2-relaxometry at 3 Tesla: a feasibility and reproducibility study.

OBJECTIVE: T2-relaxometry could differentiate between physiological and haemorrhagic joint effusion (≥ 5% blood) in vitro. Are quantitative T2-relaxation time measurements of synovial fluid feasible and reproducible in vivo in clinically bleed-free joints of men with haemophilia? MATERIALS AND METHODS: In this cross-sectional study, we measured T2-relaxation times of synovial fluid in clinically bleed-free ankles, knees or elbows of men with severe haemophilia A using a T2-mapping sequence (duration ≤ 7 min) at 3 Tesla MRI. Manual and circular regions of interest (ROI) were drawn in the synovial fluid of each joint by two independent observers to measure T2-relaxation times. Measurement feasibility was expressed as the success rate of the measurements by both observers. The interobserver and intraobserver reproducibility of the measurements were evaluated by the intraclass correlation coefficient of absolute agreement (ICC) and the limits of agreement (LoA) from Bland Altman analysis. RESULTS: We evaluated 39 clinically bleed-free joints (11 ankles, 12 knees, 16 elbows) of 39 men (median age, 24 years; range 17-33) with severe haemophilia A. The success rate of the T2-measurements was ≥ 90%. Interobserver reliability was good to excellent (manual ROI: ICC = 0.92, 95% CI 0.76-0.97; circular ROI: ICC = 0.82, 95% CI 0.66-0.91) and interobserver agreement was adequate (manual ROI: LoA = 71 ms; circular ROI: LoA = 146 ms). Intraobserver reliability was good to excellent (manual ROI: ICC = 0.78, 95% CI - 0.06-0.94; circular RO: ICC = 0.99, 95% CI 0.98-0.99) and intraobserver agreement was good (manual ROI: LoA = 63 ms; circular ROI: LoA = 41 ms). CONCLUSION: T2-relaxometry of synovial fluid in haemophilia patients is feasible with good interobserver and intraobserver reproducibility.

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)

Proteome and phospholipidome interrelationship of synovial fluid-derived extracellular vesicles in equine osteoarthritis: An exploratory 'multi-omics' study to identify composite biomarkers.

Osteoarthritis causes progressive joint deterioration, severe morbidity, and reduced mobility in both humans and horses. Currently, osteoarthritis is diagnosed at late stages through clinical examination and radiographic imaging, hence it is challenging to address and provide timely therapeutic interventions to slow disease progression or ameliorate symptoms. Extracellular vesicles are cell-derived vesicles that play a key role in cell-to-cell communication and are potential sources for specific composite biomarker panel discovery. We here used a multi-omics strategy combining proteomics and phospholipidomics in an integral approach to identify composite biomarkers associated to purified extracellular vesicles from synovial fluid of healthy, mildly and severely osteoarthritic equine joints. Although the number of extracellular vesicles was unaffected by osteoarthritis, proteome profiling of extracellular vesicles by mass spectrometry identified 40 differentially expressed proteins (non-adjusted p < 0.05) in osteoarthritic joints associated with 7 significant canonical pathways in osteoarthritis. Moreover, pathway analysis unveiled changes in disease and molecular functions during osteoarthritis development. Phospholipidome profiling by mass spectrometry showed a relative increase in sphingomyelin and a decrease in phosphatidylcholine, phosphatidylinositol, and phosphatidylserine in extracellular vesicles derived from osteoarthritic joints compared to healthy joints. Unsupervised data integration revealed positive correlations between the proteome and the phospholipidome. Comprehensive analysis showed that some phospholipids and their related proteins increased as the severity of osteoarthritis progressed, while others decreased or remained stable. Altogether our data show interrelationships between synovial fluid extracellular vesicle-associated phospholipids and proteins responding to osteoarthritis pathology and which could be explored as potential composite diagnostic biomarkers of disease.