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A normative study of the synovial fluid proteome from healthy porcine knee joints.

ABSTRACT: Synovial fluid in an articulating joint contains proteins derived from the blood plasma and proteins that are produced by cells within the joint tissues, such as synovium, cartilage, ligament, and meniscus. The proteome composition of healthy synovial fluid and the cellular origins of many synovial fluid components are not fully understood. Here, we present a normative proteomics study using porcine synovial fluid. Using our optimized method, we identified 267 proteins with high confidence in healthy synovial fluid. We also evaluated mRNA expression data from tissues that can contribute to the synovial fluid proteome, including synovium, cartilage, blood, and liver, to better estimate the relative contributions from these sources to specific synovial fluid components. We identified 113 proteins in healthy synovial fluid that appear to be primarily derived from plasma transudates, 37 proteins primarily derived from synovium, and 11 proteins primarily derived from cartilage. Finally, we compared the identified synovial fluid proteome to the proteome of human plasma, and we found that the two body fluids share many similarities, underlining the detected plasma derived nature of many synovial fluid components. Knowing the synovial fluid proteome of a healthy joint will help to identify mechanisms that cause joint disease and pathways involved in disease progression.

SUBMITTER: Bennike T

PROVIDER: S-EPMC4184458 | biostudies-literature | 2014 Oct

REPOSITORIES: biostudies-literature

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A normative study of the synovial fluid proteome from healthy porcine knee joints.

Bennike Tue T Ayturk Ugur U Haslauer Carla M CM Froehlich John W JW Proffen Benedikt L BL Barnaby Omar O Birkelund Svend S Murray Martha M MM Warman Matthew L ML Stensballe Allan A Steen Hanno H

Journal of proteome research 20140903 10

Synovial fluid in an articulating joint contains proteins derived from the blood plasma and proteins that are produced by cells within the joint tissues, such as synovium, cartilage, ligament, and meniscus. The proteome composition of healthy synovial fluid and the cellular origins of many synovial fluid components are not fully understood. Here, we present a normative proteomics study using porcine synovial fluid. Using our optimized method, we identified 267 proteins with high confidence in he ...[more]

PMID: 25160569

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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.

Project description:BackgroundMusculoskeletal ultrasound is a well accessible technique to assess disease activity in children with juvenile idiopathic arthritis. Knowledge of reference values of joint structures is indispensable to differentiate between physiological and pathological finding. The aim of this study was to assess the structural sonographic features of joints and tendons in healthy children from several age groups (0.2-18 year), and develop a set of normative data.MethodsGreyscale ultrasound was performed in 500 healthy children (age 0.2-18 years) according to a predefined scanning protocol (Additional file 1) including the shoulder, elbow, wrist, second metacarpophalangeal joint, hip, knee, ankle, and first metatarsophalangeal joint). Demographic data and values of cartilage thickness, tendon diameters, and the degree of capsular distention measured by bone-capsular distance (BCD) were collected. Differences according to the sex were assessed by unpaired t-test. Single and multiple regression analyses were performed between the ultrasound outcomes and covariates such as age, height, weight and body mass index. Growth charts and tables were developed with respect to age. Nonparametric quantile regression was applied using the R-packages quantreg and quantregGrowth.ResultsA total of 195 male and 305 female volunteers were included between the age of 0 and 18 years (mean age 8.9; range: 0.2-17.9 years). Cartilage diminished markedly as children aged, and cartilage of the boys was significantly thicker compared to the girls in all joints (p < 0.001). In addition, cartilage became thinner as children's height and weight increased (beta regression coefficients between - 0.27 and - 0.01, p < 0.0001). Capsular distention (i.e., BCD > 0 mm) was uncommon in the ankle, wrist and MCP2 (resp. in 3, 6, and 3% of cases). It was more common in the suprapatellar and parapatellar knee, MTP1 and posterior recess of the elbow (resp. in 34, 32, 46, and 39% of cases). In the hip, some capsular distention was always present. Age was found to be the best predictor for BCD (beta regression coefficients between 0.05 and 0.13, p < 0.0001). Height was, in addition to age, a good predictor of tendon diameter (beta regression coefficients between 0.03 and 0.14, p < 0.0001). Growth curves and tables for each variable were developed.ConclusionsReference values of sonographic cartilage thickness, BCD and diameters of tendons at several joints were established from 500 healthy children, aged between 0.2 and 18 years. Growth charts and tables were developed to distinguish normal findings from pathology in children with complaints suspicious of arthritis.

Dataset Information

A normative study of the synovial fluid proteome from healthy porcine knee joints.

Publications

A normative study of the synovial fluid proteome from healthy porcine knee joints.

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