Dataset Information

The change of synovial fluid proteome in rabbit surgery-induced model of knee osteoarthritis.

ABSTRACT: 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.

SUBMITTER: Luo Q

PROVIDER: S-EPMC6079142 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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The change of synovial fluid proteome in rabbit surgery-induced model of knee osteoarthritis.

Luo Qinglu Q Qin Xi X Qiu Yaxian Y Hou Lingying L Yang Ning N

American journal of translational research 20180715 7

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 an ...[more]

PMID: 30093946

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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: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-1?, IL-6, TNF-?, 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-1? 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-? expression. The VAS correlated positively with age, K-L grade, and the WOMAC score but negatively with ROM and levels of IL-1?, IL-6 and TNF-?. 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-1?, IL-6 and TNF-? 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.

Project description:Osteoarthritis (OA) is the most common musculoskeletal disorder. Although joint replacement remains the standard of care for knee OA patients, knee joint distraction (KJD), which works by temporarily off-loading the joint for 6-8 weeks, is becoming a novel joint-sparing alternative for younger OA sufferers. The biological mechanisms behind KJD structural improvements remain poorly understood but likely involve joint-resident regenerative cells including multipotent stromal cells (MSCs). In this study, we hypothesized that KJD leads to beneficial cartilage-anabolic and anti-catabolic changes in joint-resident MSCs and investigated gene expression profiles of synovial fluid (SF) MSCs following KJD as compared with baseline. To obtain further insights into the effects of local biomechanics on MSCs present in late OA joints, SF MSC gene expression was studied in a separate OA arthroplasty cohort and compared with subchondral bone (SB) MSCs from medial (more loaded) and lateral (less loaded) femoral condyles from the same joints. In OA arthroplasty cohort (n = 12 patients), SF MSCs expressed lower levels of ossification- and hypotrophy-related genes [bone sialoprotein (IBSP), parathyroid hormone 1 receptor (PTH1R), and runt-related transcription factor 2 (RUNX2)] than did SB MSCs. Interestingly, SF MSCs expressed 5- to 50-fold higher levels of transcripts for classical extracellular matrix turnover molecules matrix metalloproteinase 1 (MMP1), a disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS5), and tissue inhibitor of metalloproteinase-3 (TIMP3), all (p < 0.05) potentially indicating greater cartilage remodeling ability of OA SF MSCs, compared with SB MSCs. In KJD cohort (n = 9 patients), joint off-loading resulted in sustained, significant increase in SF MSC colonies' sizes and densities and a notable transcript upregulation of key cartilage core protein aggrecan (ACAN) (weeks 3 and 6), as well as reduction in pro-inflammatory C-C motif chemokine ligand 2 (CCL2) expression (weeks 3 and 6). Additionally, early KJD changes (week 3) were marked by significant increases in MSC chondrogenic commitment markers gremlin 1 (GREM1) and growth differentiation factor 5 (GDF5). In combination, our results reveal distinct transcriptomes on joint-resident MSCs from different biomechanical environments and show that 6-week joint off-loading leads to transcriptional changes in SF MSCs that may be beneficial for cartilage regeneration. Biomechanical factors should be certainly considered in the development of novel MSC-based therapies for OA.

Dataset Information

The change of synovial fluid proteome in rabbit surgery-induced model of knee osteoarthritis.

Publications

The change of synovial fluid proteome in rabbit surgery-induced model of knee osteoarthritis.

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