Dataset Information

Leucocyte Abnormalities in Synovial Fluid of Degenerative and Inflammatory Arthropathies.

ABSTRACT: Genome damage has been related to the induction of autoimmune processes, chronic inflammation, and apoptosis. Recent studies suggest that some rheumatological diseases are associated with overall genomic instability in the T cell compartment. However, no data regarding leucocyte abnormalities in synovial fluid (SF) and their relationship with inflammation are available. The aim of this study was to investigate cellular phenotypes in SF collected from patients with different inflammatory arthropathies, including rhematoid arthritis (RA), psoriatic arthritis (PsA), crystal-induced arthritis (CIA), and non-inflammatory arthropathies, such as osteoarthritis (OA). We found high percentage of micronuclei in SF from CIA compared to the other groups and a high frequency of pyknotic cell in RA and CIA patients. A correlation between pyknosis and immature polymorphonuclear cells with local inflammatory indices was observed. The study of the apoptosis process revealed an increased BAX expression in CIA and RA compared to OA and PsA, while Bcl-2 was higher in CIA. Caspase-3 activity was increased in SF from RA patients and correlates with inflammatory and anti-inflammatory cytokines. In conclusion, our results showed that inflammatory SF is associated with genomic instability and abnormal cell subsets.

SUBMITTER: Baggio C

PROVIDER: S-EPMC10056596 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature

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Leucocyte Abnormalities in Synovial Fluid of Degenerative and Inflammatory Arthropathies.

Baggio Chiara C Luisetto Roberto R Boscaro Carlotta C Scanu Anna A Ramonda Roberta R Albiero Mattia M Sfriso Paolo P Oliviero Francesca F

International journal of molecular sciences 20230313 6

Genome damage has been related to the induction of autoimmune processes, chronic inflammation, and apoptosis. Recent studies suggest that some rheumatological diseases are associated with overall genomic instability in the T cell compartment. However, no data regarding leucocyte abnormalities in synovial fluid (SF) and their relationship with inflammation are available. The aim of this study was to investigate cellular phenotypes in SF collected from patients with different inflammatory arthropa ...[more]

PMID: 36982526

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Project description:ObjectiveTo evaluate the degree of knee fat pad abnormalities after acute anterior cruciate ligament (ACL) tear via magnetic resonance fat pad scoring and to assess cross-sectionally its association with synovial fluid biomarkers and with early cartilage damage as quantified via T1ρ and T2 relaxation time measurements.Design26 patients with acute ACL tears underwent 3T MR scanning of the injured knee prior to ACL reconstruction. The presence and degree of abnormalities of the infrapatellar (IPFP) and the suprapatellar (SPFP) fat pads were scored on MR images along with grading of effusion-synovitis and synovial proliferations. Knee cartilage composition was assessed by 3T MR T1ρ and T2 mapping in six knee compartments. We quantified concentrations of 20 biomarkers in synovial fluid aspirated at the time of ACL reconstruction. Spearman rank partial correlations with adjustments for age and gender were employed to evaluate correlations of MR, particularly cartilage composition and fat pad abnormalities, and biomarker data.ResultsThe degree of IPFP abnormality correlated positively with the synovial levels of the inflammatory cytokine markers IFN-γ (ρpartial = 0.64, 95% CI (0.26-0.85)), IL-10 (ρpartial = 0.47, 95% CI (0.04-0.75)), IL-6 (ρpartial = 0.56, 95% CI (0.16-0.81)), IL-8 (ρpartial = 0.49, 95% CI (0.06-0.76)), TNF-α (ρpartial = 0.55, 95% CI (0.14-0.80)) and of the chondrodestructive markers MMP-1 and -3 (MMP-1: ρpartial = 0.57, 95% CI (0.17-0.81); MMP-3: ρpartial = 0.60, 95% CI (0.21-0.83)). IPFP abnormalities were significantly associated with higher T1ρ and T2 values in the trochlear cartilage (T1ρ: ρpartial = 0.55, 95% CI (0.15-0.80); T2: ρpartial = 0.58, 95% CI (0.18-0.81)) and with higher T2 values in the medial femoral, medial tibial as well as in patellar cartilage (0.45 ≤ ρpartial ≤ 0.59). Correlations between SPFP abnormalities and synovial markers were not significant except for IL-6 (ρpartial = 0.57, 95% CI (0.17-0.81)).ConclusionsThis exploratory study suggests that acute ACL rupture can be associated with damage to knee tissues such as the inferior fat pad of the knee. Such fat pad injury could be partially responsible for the apparent post-injury pro-inflammatory response noted in ACL-injured individuals. However, future longitudinal studies are needed to link ACL-rupture associated fat pad injury with important patient outcomes such as the development of posttraumatic osteoarthritis.

Project description:Changes in cellular metabolism have been implicated in mediating the activated fibroblast phenotype in a number of chronic inflammatory disorders, including pulmonary fibrosis, renal disease and rheumatoid arthritis. The aim of this study was therefore to characterise the metabolic profile of synovial joint fluid and synovial fibroblasts under both basal and inflammatory conditions in a cohort of obese and normal-weight hip OA patients. Furthermore, we sought to ascertain whether modulation of a metabolic pathway in OA synovial fibroblasts could alter their inflammatory activity. Synovium and synovial fluid was obtained from hip OA patients, who were either of normal-weight or obese and were undergoing elective joint replacement surgery. The synovial fluid metabolome was determined by 1H NMR spectroscopy. The metabolic profile of isolated synovial fibroblasts in vitro was characterised by lactate secretion, oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) using the Seahorse XF Analyser. The effects of a small molecule pharmacological inhibitor and siRNA targeted at glutaminase-1 (GLS1) were assessed to probe the role of glutamine metabolism in OA synovial fibroblast function. Obese OA patient synovial fluid (n = 5) exhibited a different metabotype, compared to normal-weight patient fluid (n = 6), with significantly increased levels of 1, 3-dimethylurate, N-Nitrosodimethylamine, succinate, tyrosine, pyruvate, glucose, glycine and lactate, and enrichment of the glutamine-glutamate metabolic pathway, which correlated with increasing adiposity. In vitro, isolated obese OA fibroblasts exhibited greater basal lactate secretion and aerobic glycolysis, and increased mitochondrial respiration when stimulated with pro-inflammatory cytokine TNFα, compared to fibroblasts from normal-weight patients. Inhibition of GLS1 attenuated the TNFα-induced expression and secretion of IL-6 in OA synovial fibroblasts. These findings suggest that altered cellular metabolism underpins the inflammatory phenotype of OA fibroblasts, and that targeted inhibition of glutamine-glutamate metabolism may provide a route to reducing the pathological effects of joint inflammation in OA patients who are obese.

Project description:ObjectivesTo compare the proteomics of synovial fluid (SF)-derived exosomes in rheumatoid arthritis (RA), axial spondyloarthritis (axSpA), gout, and osteoarthritis (OA) patients.MethodsExosomes were separated from SF by the Exoquick kit combined ultracentrifugation method. Tandem mass tags (TMT)-labeled liquid chromatography mass spectrometry (LC-MS/MS) technology was used to analyze the proteomics of SF-derived exosomes. Volcano plot, hierarchical cluster, gene ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were conducted.ResultsA total of 1,678 credible proteins were detected. Sixty-nine differentially expressed proteins were found in gout, compared with OA, axSpA, and RA simultaneously. Twenty-five proteins were found highly expressed in gout uniquely, lysozyme C and protein S100-A9 included, whose bioinformatic analysis was significantly involved in "neutrophil degranulation" and "prion diseases". Eighty-four differentially expressed proteins were found in axSpA, compared with OA, gout, and RA simultaneously. Thirty-nine proteins were found highly expressed in axSpA uniquely, RNA-binding protein 8A and protein transport protein Sec24C included, whose bioinformatic analysis was significantly involved in "acute-phase response" and "citrate cycle". One hundred and eighty-four differentially expressed proteins were found in RA, compared with OA, gout, and axSpA simultaneously. Twenty-eight proteins were found highly expressed in RA uniquely, pregnancy zone protein (PZP) and stromelysin-1 included, whose bioinformatic analysis was significantly involved in "serine-type endopeptidase inhibitor activity" and "complement and coagulation cascades". Enzyme-linked immunosorbent assay (ELISA) result showed that the exosome-derived PZP level of SF in RA was higher than that in OA (p < 0.05).ConclusionOur study for the first time described the protein profiles of SF-derived exosomes in RA, axSpA, gout, and OA patients. Some potential biomarkers and hypothetical molecular mechanisms were proposed, which may provide helpful diagnostic and therapeutic insights for inflammatory arthritis (IA).

Project description:BackgroundInflammatory mediators in the synovial fluid (SF) play critical roles in the initiation and development of pain in knee osteoarthritis (KOA). However, data for inflammatory marker expression are conflicting, and the role of SF inflammatory mediators in neuropathic pain is not clear. Therefore, the aim of this study was to identify SF inflammatory mediators associated with nociceptive and neuropathic pain in KOA.MethodsLevels of IL-1β, IL-6, TNF-α, macrophage colony-stimulating factor, MMP-3, MMP-13, metalloproteinase with thrombospondin motifs 5, calcitonin gene-related peptide, neuropeptide Y, substance P and bradykinin were measured using enzyme-linked immunosorbent assays in 86 patients. Nociceptive pain was assessed using the numeric rating scale (NRS), visual analog scale (VAS) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score. Neuropathic pain was determined using the PainDETECT questionnaire. Moreover, knee function was evaluated by the WOMAC score and range of motion (ROM) assessments. Radiological grade was defined using the Kellgren-Lawrence (K-L) grading scale.ResultsPain scores measured using different methods correlated highly with each other. A worse K-L grade and knee function were associated with worse pain. Expression of IL-1β and IL-6 was increased in the early stage compared with the late stage. The NRS score correlated positively with age, K-L grade, and the WOMAC score and negatively with ROM and TNF-α expression. The VAS correlated positively with age, K-L grade, and the WOMAC score but negatively with ROM and levels of IL-1β, IL-6 and TNF-α. The WOMAC pain score did not correlate with any of the inflammatory mediators measured; it correlated only with ROM. The PainDETECT score correlated only with the WOMAC score. Expression of other inflammatory mediators did not correlate with any of the pain scores.ConclusionsIL-1β, IL-6 and TNF-α play critical roles in pain in the early stage of KOA and correlate with pain. The catabolic enzymes and neuropeptides measured do not correlate with nociceptive and neuropathic pain. New biomarkers related to pain in the late stage need to be further investigated.

Dataset Information

Leucocyte Abnormalities in Synovial Fluid of Degenerative and Inflammatory Arthropathies.

Publications

Leucocyte Abnormalities in Synovial Fluid of Degenerative and Inflammatory Arthropathies.

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