Proteomic analysis of synovial fluid: current and potential uses to improve clinical outcomes

Peffers, Mandy J.; Smagul, Aibek; Anderson, James

doi:10.1080/14789450.2019.1578214

Cited by 23 publications

(28 citation statements)

References 166 publications

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“…greatly enhancing the information that can be obtained from separate analyses (113). However, this poses the challenge of developing multi 'omic' integration techniques.…”

Section: Computational Integration Of Separate 'Omics' Datasets Can Wmentioning

confidence: 99%

Metabolomic and Proteomic Stratification of Equine Osteoarthritis

Anderson

Phelan

Caamaño-Gutiérrez

et al. 2020

Preprint

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Osteoarthritis (OA) is characterised by loss of articular cartilage, synovial membrane dysfunction and subchondral sclerosis. Few studies have used a global approach to stratify equine synovial fluid (SF) molecular profiles according to OA severity. SF was collected from 58 metacarpophalangeal (MCP) and metatarsophalangeal joints of racing Thoroughbred horses (Hong Kong Jockey Club; HKJC) and 83 MCP joints of mixed breed horses from an abattoir and equine hospital (biobank). Joints were histologically and macroscopically assessed for OA severity. For proteomic analysis, native SF and SF loaded onto ProteoMiner™ equalisation columns, to deplete high abundant proteins, were analysed using liquid chromatography-tandem mass spectrometry (LC-MS/MS) and label-free quantification. Validation of selected differentially expressed proteins was undertaken using clinical SF collected during diagnostic investigations. Native SF metabolites were analysed using 1D 1H Nuclear Magnetic Resonance (NMR). 1,834 proteins and 40 metabolites were identified in equine SF. Afamin levels decreased with synovitis severity and four uncharacterised proteins decreased with OA severity. Gelsolin and lipoprotein binding protein decreased with OA severity and apolipoprotein A1 levels increased for mild and moderate OA. Within the biobank, glutamate levels decreased with OA severity and for the HKJC cohort, 2-aminobutyrate, alanine and creatine increased with severity. Proteomic and metabolomic integration was undertaken using linear regression via Lasso penalisation modelling, incorporating 29 variables (R2=0.82) with principal component 2 able to discriminate advanced OA from earlier stages, predominantly driven by H9GZQ9, F6ZR63 and alanine. Combining biobank and HKJC datasets, discriminant analysis of principal components modelling prediction was good for mild OA (90%). This study has stratified equine OA using both metabolomic and proteomic SF profiles and identified a panel of markers of interest which may be applicable to grading OA severity. This is also the first study to undertake computational integration of NMR metabolomic and LC-MS/MS proteomic datasets of any biological system.

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“…greatly enhancing the information that can be obtained from separate analyses (113). However, this poses the challenge of developing multi 'omic' integration techniques.…”

Section: Computational Integration Of Separate 'Omics' Datasets Can Wmentioning

confidence: 99%

Metabolomic and Proteomic Stratification of Equine Osteoarthritis

Anderson

Phelan

Caamaño-Gutiérrez

et al. 2020

Preprint

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“…During OA pathology, disease-associated peptide fragments (neopeptides) are generated from cartilage breakdown due to increased enzymatic activity/abundance of MMPs, ADAMTSs, cathepsins and serine proteases [28][29][30] . MS analysis of these neopeptides can then be applied to identify potential early OA biomarkers 31 . Previously a murine 32 amino acid peptide fragment, generated through increased activity of MMP and ADAMTS-4/5 and subsequent aggrecan degradation, was found to drive OA pain via Toll-like receptor 2 32 .…”

Section: Introductionmentioning

confidence: 99%

“…Neopeptide targeting therefore has the potential to provide a localised analgesic at the site of joint degeneration 31 . Numerous equine OA studies investigating both synovial fluid (SF) and cartilage have identified potential neopeptides of interest 28,[33][34][35] .…”

Section: Introductionmentioning

confidence: 99%

“…Numerous equine OA studies investigating both synovial fluid (SF) and cartilage have identified potential neopeptides of interest 28,[33][34][35] . Development of antibodies targeted to OA specific neopeptides would provide the ability to monitor cartilage degeneration, assess therapeutic response and potentially provide future novel therapeutic targets 31,36 .…”

Section: Introductionmentioning

confidence: 99%

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Ex-VivoEquine Cartilage Explant Osteoarthritis Model - A Metabolomics and Proteomics Study

Anderson

Phelan

Foddy

et al. 2020

Preprint

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Osteoarthritis (OA) is an age-related degenerative musculoskeletal disease characterised by loss of articular cartilage, synovitis, abnormal bone proliferation and subchondral bone sclerosis. Underlying OA pathogenesis is yet to be fully elucidated with no OA specific biomarkers in clinical use. Ex-vivo equine cartilage explants (n=5) were incubated in TNFα/IL-1β supplemented culture media for 8 days, with media removed and replaced at 2, 5 and 8 days. Acetonitrile metabolite extractions of 8 day cartilage explants and media samples at all time points underwent 1D 1 H nuclear magnetic resonance metabolomic analysis with media samples also undergoing mass spectrometry proteomic analysis.Within the cartilage, metabolites glucose and lysine were elevated following TNF-α/IL-1β treatment whilst adenosine, alanine, betaine, creatine, myo-inositol and uridine levels decreased. Within the culture media, four, four and six differentially abundant metabolites and 154, 138 and 72 differentially abundant proteins, with > 2 fold change, were identified for 1-2 day, 3-5 day and 6-8 day time points respectively. Nine potential novel OA neopeptides were elevated in treated media. Our innovative study has identified differentially abundant metabolites, proteins and extracellular matrix derived neopeptides, providing insightful information on OA pathogenesis, enabling potential translation for clinical markers and possible new therapeutic targets.

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“…In contrast, the global crosstalk between molecules could be very informative in order to explore and gain deeper insights into the molecular pathogenesis of OA 12 . While a number of different omics studies have been carried out [13][14][15][16][17][18][19] , they were limited by the technologies used or availability of biological samples. Therefore, the aim of this study was to explore disease stages of OA using a global discovery approach based on state-of-the-art mass spectrometry (MS) instrumentation and methodology.…”

Section: Introductionmentioning

confidence: 99%

Proteomics profiling of human synovial fluid suggests global increased protein interplay in early-osteoarthritis (OA) and lost in late-stage OA

Ali

Turkiewicz

Hughes

et al. 2020

Preprint

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The underlying molecular mechanisms in osteoarthritis (OA) development are largely unknown. This study explores the proteome and the pairwise interplay of proteins on a global level in synovial fluid from patients with late-stage knee OA (arthroplasty), early knee OA (arthroscopy due to degenerative meniscal tear) and from controls without knee OA. Synovial fluid samples were analyzed using state-of-the-art mass spectrometry with data-independent acquisition. The differential expression of the proteins detected was clustered and evaluated with data mining strategies and a multilevel model. Group-specific slopes of associations were estimated between expressions of each pair of identified proteins to assess the co-expression (i.e. interplay) between the proteins in each group. The differential expression revealed more proteins to be increased in early-OA vs controls than late-stage OA vs controls. For most of these proteins, the fold changes between late-stage OA vs controls and early-stage OA vs controls were remarkably similar suggesting potential involvement in the OA process. Further, for the first time, this study illustrated distinct patterns in protein co-expression suggesting that the global interplay between the protein machinery is increased in early-OA and lost in late-stage OA. Further efforts should probably focus on earlier stages of the disease than previously considered.

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Proteomic analysis of synovial fluid: current and potential uses to improve clinical outcomes

Cited by 23 publications

References 166 publications

Metabolomic and Proteomic Stratification of Equine Osteoarthritis

Metabolomic and Proteomic Stratification of Equine Osteoarthritis

Ex-VivoEquine Cartilage Explant Osteoarthritis Model - A Metabolomics and Proteomics Study

Proteomics profiling of human synovial fluid suggests global increased protein interplay in early-osteoarthritis (OA) and lost in late-stage OA

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