Pain in hand osteoarthritis is associated with crystals in the synovial fluid: a cross-sectional study of people with hand osteoarthritis undergoing surgery.
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ABSTRACT:
SUBMITTER: Dossing A
PROVIDER: S-EPMC10450056 | biostudies-literature | 2023 Aug
REPOSITORIES: biostudies-literature
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Pain in hand osteoarthritis is associated with crystals in the synovial fluid: a cross-sectional study of people with hand osteoarthritis undergoing surgery.
Døssing Anna A Conaghan Philip G PG K Stamp Lisa L M McCarthy Geraldine G Henriksen Marius M Christensen Robin R Terslev Lene L Ellegaard Karen K Henrik Søe Niels N Juul Lars L Hansen Philip P Radev Dimitar Ivanov DI Nybing Janus Damm JD Boesen Mikael M Bliddal Henning H
RMD open 20230801 3
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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.
| S-EPMC7023718 | biostudies-literature
Project description:The aims of this study were to explore the change of synovial fluid (SF) proteome in a knee osteoarthritis (KOA) rabbit model, and to provide a new target for the treatment of knee osteoarthritis at the proteomic level. Sixteen New Zealand rabbits were randomly and equally divided into two groups. Group A rabbits were subjected to right anterior cruciate ligament transection (ACLT), while group B rabbits were subjected to sham ACLT. Six weeks later, the proteomes of knee joint SF from group A and B rabbits were analyzed using a label-free quantitative proteomic analysis method. We extracted 944 relevant items from GO BlastGO2 for the 23 proteins differentially expressed between the two groups. The final annotation results were 23 protein sequences annotated by 462 GO items. According to the KEGG gene database of rabbit protein sequences, as well as annotation of the KO numbers of homologous/similar proteins to the relevant 64 KEGG pathways, we extracted the sequences of 16 significantly differently expressed proteins among the relevant 64 KEGG messages/metabolism pathways. These included adiponectin, pyruvate kinase, bisphosphoglycerate mutase, HtpG/heat shock proteins, hemoglobin subunit alpha-1 2, VCP (CDC48), 14-3-3 protein beta/theta/zeta, and ferritin heavy chain, whose levels were decreased in group A. The other proteins were fibrinogen alpha/beta/gamma chain, carboxylesterase 2, paraoxonase/arylesterase 1, apolipoprotein A-I, immunoglobulin heavy chain, and transferrin, whose levels were increased in group B. The identified differentially expressed proteins indicate the change of SF proteomic expression in KOA and may provide protein targets for treating this condition.
| S-EPMC6079142 | biostudies-literature
Project description:BACKGROUND:Osteoarthritis is a chronic musculoskeletal disorder characterized mainly by progressive degradation of the hyaline cartilage. Patients with osteoarthritis often postpone seeking medical help, which results in the diagnosis being made at an advanced stage of cartilage destruction. Sustained efforts are needed to identify specific markers that might help in early diagnosis, monitoring disease progression and in improving therapeutic outcomes. We employed a multipronged proteomic approach, which included multiple fractionation strategies followed by high resolution mass spectrometry analysis to explore the proteome of synovial fluid obtained from osteoarthritis patients. In addition to the total proteome, we also enriched glycoproteins from synovial fluid using lectin affinity chromatography. RESULTS:We identified 677 proteins from synovial fluid of patients with osteoarthritis of which 545 proteins have not been previously reported. These novel proteins included ADAM-like decysin 1 (ADAMDEC1), alanyl (membrane) aminopeptidase (ANPEP), CD84, fibulin 1 (FBLN1), matrix remodelling associated 5 (MXRA5), secreted phosphoprotein 2 (SPP2) and spondin 2 (SPON2). We identified 300 proteins using lectin affinity chromatography, including the glycoproteins afamin (AFM), attractin (ATRN), fibrillin 1 (FBN1), transferrin (TF), tissue inhibitor of metalloproteinase 1 (TIMP1) and vasorin (VSN). Gene ontology analysis confirmed that a majority of the identified proteins were extracellular and are mostly involved in cell communication and signaling. We also confirmed the expression of ANPEP, dickkopf WNT signaling pathway inhibitor 3 (DKK3) and osteoglycin (OGN) by multiple reaction monitoring (MRM) analysis of osteoarthritis synovial fluid samples. CONCLUSIONS:We present an in-depth analysis of the synovial fluid proteome from patients with osteoarthritis. We believe that the catalog of proteins generated in this study will further enhance our knowledge regarding the pathophysiology of osteoarthritis and should assist in identifying better biomarkers for early diagnosis.
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Project description:The role of calcium pyrophosphate (CPP) crystals in osteoarthritis (OA) is still a matter of debate. With this study we aimed to investigate the inflammatory features of synovial fluid (SF) collected from patients with OA with CPP crystals compared with those without crystals. We also explored the effect of OA SF on monocytes response. SFs were collected from adult patients with OA and subdivided according to the presence of crystals. Local cellular and humoral inflammatory mediators were analysed in the SF samples. The expression levels of IL-1β, IL-18, CASP-1, NLRP3, and GAPDH were measured by RT-PCR in the cells obtained by pelleting the SF samples. For the in vitro study, a monocytic cell line was treated with selected SF samples. SF with CPP crystals showed a significant increase in inflammatory cellular indices and higher levels of IL-1β, IL-8, and caspase-1 transcript with respect to SF without crystals. Higher concentrations of VEGF were also observed in the early stages of the whole OA patients. THP-1 cells stimulated with OA SF released a significant amount of IL-1 β in culture supernatants. This study demonstrated that SF collected from patients with OA shows different inflammatory features depending on the presence of CPP crystals.
| S-EPMC10778695 | biostudies-literature
Project description:Surgical transection of the anterior cruciate ligament (ACL) in the porcine model leads to posttraumatic osteoarthritis if left untreated. However, a recently developed surgical treatment, bridge-enhanced ACL repair, prevents further cartilage damage. Since the synovial fluid bathes all the intrinsic structures of knee, we reasoned that a comparative analysis of synovial fluid protein contents could help to better understand the observed chondroprotective effects of the bridge-enhanced ACL repair. We hypothesized that post-surgical changes in the synovial fluid proteome would be different in the untreated and repaired knees, and those changes would correlate with the degree of cartilage damage. Thirty adolescent Yucatan mini-pigs underwent unilateral ACL transection and were randomly assigned to either no further treatment (ACLT, n = 14) or bridge-enhanced ACL repair (BEAR, n = 16). We used an isotopically labeled high resolution LC MS/MS-based proteomics approach to analyze the protein profile of synovial fluid at 6 and 12 months after ACL transection in untreated and repaired porcine knees. A linear mixed effect model was used to compare the normalized protein abundance levels between the groups at each time point. Bivariate linear regression analyses were used to assess the correlations between the macroscopic cartilage damage (total lesion area) and normalized abundance levels of each of the identified secreted proteins. There were no significant differences in cartilage lesion area or quantitative abundance levels of the secreted proteins between the ACLT and BEAR groups at 6 months. However, by 12 months, greater cartilage damage was seen in the ACLT group compared to the BEAR group (p = 0.005). This damage was accompanied by differences in the abundance levels of secreted proteins, with higher levels of Vitamin K-dependent protein C (p = 0.001), and lower levels of Apolipoprotein A4 (p = 0.021) and Cartilage intermediate layer protein 1 (p = 0.049) in the ACLT group compared to the BEAR group. There were also group differences in the secreted proteins that significantly changed in abundance between 6 and 12 months in ACLT and BEAR knees. Increased concentration of Ig lambda-1 chain C regions and decreased concentration of Hemopexin, Clusterin, Coagulation factor 12 and Cartilage intermediate layer protein 1 were associated with greater cartilage lesion area. In general, ACLT knees had higher concentrations of pro-inflammatory proteins and lower concentrations of anti-inflammatory proteins than BEAR group. In addition, the ACLT group had a lower and declining synovial concentrations of CILP, in contrast to a consistently high abundance of CILP in repaired knees. These differences suggest that the knees treated with bridge-enhanced ACL repair may be maintaining an environment that is more protective of the extracellular matrix, a function which is not seen in the ACLT knees.
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Project description:In this study, blood was collected from human participants with osteoarthritis pain, along with radiographic scores (Kellgren & Lawrence Score (KL)) and pain scores (Numerical Rating Scale (NRS)). Peripheral blood mononuclear cells were isolated from whole blood, and classical and intermediate monocytes were further isolated using fluorescence-activated cell sorting. mRNA was then extracted from monocytes for sequencing.
2024-12-31 | E-MTAB-14402 | biostudies-arrayexpress
Project description:ObjectiveTo examine the relation of sleep problems to pain outcomes in people with hand osteoarthritis, and the extent to which central sensitization mediates these relationships.DesignIn total 299 participants from the Nor-Hand cohort study rated their sleep problems (no, slight, moderate or severe problems), hand pain intensity on a Numeric Rating Scale (NRS, range: 0-10) and Australian/Canadian Osteoarthritis Hand Index (AUSCAN; range: 0-20), and overall bodily pain intensity (NRS). Central sensitization was evaluated by quantitative sensory testing. All pain questionnaires were repeated after 3.5 years. We explored the associations between sleep problems at baseline and pain outcomes at baseline and follow-up and fitted natural effect models to examine the extent to which measures of central sensitization mediated the effects of sleep problems on pain. All main analyses were adjusted for age, sex, education, comorbidities, and body mass index.ResultsSlight, moderate, and severe sleep problems were reported by 33.8 %, 26.8 % and 14.3 %, respectively. In general, individuals with severe versus without sleep problems reported relatively more intense pain at baseline and follow up (i.e., a 1.68 (95 % confidence interval 0.89-2.46) higher NRS hand pain at baseline). Associations between sleep and central sensitization were weak, with no mediating effects found. For example, the indirect effect of remote pressure pain thresholds was 0.06 (-0.27, 0.39) NRS points for hand pain among individuals reporting severe sleep problems.ConclusionSleep problems are commonly reported and related to pain intensity in people with hand osteoarthritis, while the underlying mechanisms and temporal relationship remain unclear.
| S-EPMC11875149 | biostudies-literature
Project description:ObjectiveTo examine whether psychological symptoms and cognitive patterns are associated with self-reported pain and pain sensitization in people with hand osteoarthritis (OA).DesignIn the Nor-Hand study (n = 300), people with hand OA self-reported psychological symptoms (Hospital Anxiety and Depression Scale), cognitive patterns (Pain catastrophizing Scale and Arthritis Self-Efficacy Scale) as well as their pain severity in hands, overall pain and multi-joint pain. Central pain sensitization was measured clinically by temporal summation and pressure pain threshold tests. We examined whether psychological symptoms and cognitive patterns were cross-sectionally associated with pain using linear regression. Beta coefficients (β) per one standard deviation of the independent variable were presented. Stratified analyses were performed in cases of significant interactions (p < 0.10).ResultsHigher levels of anxiety, depressive symptoms and pain catastrophizing and low levels of self-efficacy were statistically significantly associated with higher levels of hand pain by Numeric Rating Scale (β = 0.43, 0.48 and -0.57, respectively). Similar associations were found for overall pain, but not for measures of central pain sensitization. In stratified analyses, anxiety and depressive symptoms were more strongly related with pain in subgroups with younger age and higher comorbidity burden. Pain catastrophizing was more strongly related with pain in subgroups with younger age, overweight/obesity, higher comorbidity burden and poor sleep.ConclusionPsychological symptoms and cognitive patterns were associated with self-reported OA pain, especially in people with younger age, overweight/obesity, higher comorbidity burden and poor sleep. No associations were found for psychological symptoms and cognitive patterns with pain sensitization.
| S-EPMC9718141 | biostudies-literature
Project description:ObjectiveTo examine whether pain sensitization is associated with hand and lower extremity function in people with hand osteoarthritis (OA) in the Nor-Hand study.DesignPain sensitization was assessed by pressure pain thresholds (PPTs) and temporal summation (TS). Hand function was assessed by Australian/Canadian Osteoarthritis Hand Index (AUSCAN) (range: 0-36), grip strength and Moberg pick-up test, and lower extremity function was assessed by Western Ontario and McMaster Universities Osteoarthritis Index (range: 0-68), 30-s chair stand test, and 40-m walk test. We examined whether sex-standardized PPT and TS values were cross-sectionally associated with measures of physical function using linear regression analyses. Beta coefficients were presented per sex-specific standard deviation of PPT and TS. The mediating effect of pain was examined by causal-inference based mediation analysis.ResultsIn 206 participants, higher PPTs at/near the hand, indicative of less peripheral and/or central pain sensitization, were associated with greater grip strength and better self-reported hand function (beta for PPT at finger joint on AUSCAN function: -1.41, 95% CI -2.40, -0.42). Higher PPTs at/near the hand, near the knee and at trapezius were associated with lower extremity function, although not statistically significant for all outcomes. Self-reported pain severity mediated the effect of PPT on self-reported function. TS was not associated with hand or lower extremity function.ConclusionPeripheral sensitization, and possibly central sensitization, was associated with impaired function. Effects of PPTs on self-reported function were mediated by self-reported pain, whereas there might be a direct effect of sensitization or effects through other mediators on performance-based function.
| S-EPMC10528207 | biostudies-literature
Project description:BackgroundUltrasound (US) therapy may improve osteoarthritis symptoms. We investigated the effects of US on the synovial fluid (SF) proteome in a rabbit knee osteoarthritis (KOA) model to explore its therapeutic mechanisms.MethodsSixteen healthy 6-month-old New Zealand white rabbits (eight male, eight female), weighing 2.5-3.0 kg, were randomly divided into groups A and B with eight rabbits per group. Both groups were subjected to right anterior cruciate ligament transaction. Six weeks after surgery, we treated the operated knee joint of group A rabbits with US and of group B rabbits with sham US for 2 weeks. The proteomes of knee joint SF from groups A and B rabbits were then analyzed using a label-free mass spectrometry (MS) quantification method.ResultsWe identified 19 protein sequences annotated by 361 Gene Ontology (GO) items. According to the Kyoto Encyclopedia of Genes and Genomes (KEGG) database of rabbit protein sequences, we then annotated the KO numbers of homologous/similar proteins to 32 relevant KEGG pathways. We extracted 10 significantly differentially expressed proteins among the 32 relevant KEGG messages/metabolism pathways. The proteins whose levels were decreased were apolipoprotein A-I (AopA-1), transferrin (TF), carboxypeptidase B2 (CBP2), arylesterase/paraoxonase (PON), fibrinogen alpha chain, and alpha-2-macroglobulin (A2M). The proteins whose levels were increased were molecular chaperone HtpG/heat shock proteins (htpG, HSP90A), decorin (DCN), pyruvate kinase (PK, pyk), and fatty acid-binding protein 4/adipocyte (FABP4, aP2).ConclusionsUS therapy can alter protein levels in SF, which can decrease AopA-1, TF, CBP2, PON, fibrinogen alpha chain and A2M protein levels, and increase HtpG/HSP90A, DCN, PK/PKY, and FABP4/aP2 protein levels in SF of KOA, suggesting that the therapeutic mechanisms of US therapy on KOA may occur through changes in the SF proteome.
| S-EPMC6387552 | biostudies-literature