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Proteomic analysis of synovial fluid identifies periostin as a biomarker for anterior cruciate ligament injury

ABSTRACT: Identification of novel synovial fluid biomarkers that can differentiate early changes following ACL injury from OA using tandem-mass-spectrometry

INSTRUMENT(S): Q Exactive Plus

ORGANISM(S): Homo Sapiens (ncbitaxon:9606)

SUBMITTER: Muhammad Farooq Rai

PROVIDER: MSV000083551 | MassIVE | Mon Mar 11 05:46:00 GMT 2019

SECONDARY ACCESSION(S): PXD013043

REPOSITORIES: MassIVE

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miRNA sequencing of synovial fluid derived extracellular vesicles between normal and osteoarthritis (OA) patients

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Multiomic temporal landscape of plasma and synovial fluid derived extracellular vesicles using an experimental model of equine osteoarthritis

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Transcription profiling of rat brain time series samples treated with lateral fluid percussion injury or sham surgery without injury to investigate the physiological effects of taumatic brain injury

Project description:Traumatic brain injury (TBI) induces a complex cascade of molecular and physiological effects. This study proposes to investigate the gene expression profile in cortex and hippocampus over early time points, following two different injury severities. These results will complement prior knowledge of both metabolic and neuroplastic changes after TBI, as well as serve as a starting point to investigate additional gene families whose expression is altered after TBI.,To characterize the profile of gene expression following a diffuse traumatic brain injury of varying severity in adult rats. ,Distinct patterns of gene expression following traumatic brain injury will occur in a time- and injury-dependent fashion. In particular, changes in expression of enzymes involved in energy metabolism and neuroplasticity will be detected.,Adult rats will be subjected to mild and severe lateral fluid percussion injury OR sham surgery without injury. At various post-injury timepoints (0.5, 4 and 24 hours), animals will be sacrificed, brain regions (parietal cortex and hippocampus, ipsilateral and contralateral to injury) will be dissected and RNA isolated. RNA will be used to synthesize cRNA probes for microarray hybridization. RNA from 2 matched animals will be pooled onto a single chip (U34A rat, Affymetrix). Comparisons will be made between sham and injured animals, with brain region, injury severity, and post-injury time point as the experimental variables.

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Proteomics Reveals Increased Periostin in Synovial Fluid from Canine and Human Anterior Cruciate Ligament Injury

Project description:Post-traumatic osteoarthritis (PTOA) is a common sequela to anterior cruciate ligament (ACL) injury in humans and dogs. Identification of conserved targets between species may hasten biomarker identification and therapeutic development. To identify differentially regulated synovial fluid (SF) proteins in ACL injury, SF samples were collected from knees with ACL injury or control knees (n=8 per species) in human and dog patients. The SF proteome was evaluated using nano-scale reverse phase chromatography and tandem mass spectroscopy. Associations between proteins and ACL injury were analyzed in both species. Immunoassays were used to validate key proteins identified via mass spectrometry, including periostin, α-2-macroglublin, and lubricin, in additional SF samples (dog: n=57 ACL, n=31 controls; human: n=20 ACL, n=15 advanced OA) and plasma samples (human: n=18 ACL, n=15 advanced OA, and n=12 controls). Periostin was the most upregulated SF protein (log2 fold-change) in both dog (2.6) and human (3.5) ACL injury, followed by complement C1q (2.3) and α-2-macroglobulin (1.8) in dogs and fibrinogen (1.1) and α-2-macroglobulin (1.1) in humans. Top downregulated proteins included serum amyloid A1 (-1.9) and aggrecan (-1.8) in dogs and carbonic anhydrase 2 (-3.2) and hemoglobin subunit β (-2.8) in humans. Approximately 60% of proteins detected were shared between species, and immunoregulatory and macromolecular transport proteins were the most common families. Clinical Relevance: Findings in both species support further investigation into periostin as a potential biomarker or therapeutic target and the use of spontaneous ACL injury in dogs as a potential translational large animal model for human ACL injury.

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microRNA cerebrospinal fluid profile during the early brain injury period as a biomarker in subarachnoid hemorrhage patients

Project description:microRNA cerebrospinal fluid profile during the early brain injury period as a biomarker in subarachnoid hemorrhage patients

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

Project description: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 deceased 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. More proteins were 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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Proteolytic information flows from human knee osteoarthritic cartilage to synovial fluid and defines the roles of key drug targets -1

Project description:Objectives: Proteolytic cartilage loss is a major mechanism of osteoarthritis (OA) pathogenesis but few joint breakdown biomarkers are currently available. We sought to determine the overlap of proteolytic peptides in OA cartilage and synovial fluid on a proteome-wide scale with the goals of increasing the biomarker repertoire and for attribution to individual proteases. Design: Proteins isolated from matched human OA cartilage and synovial fluid from 5 knees were analyzed by N-terminomics using Terminal Amine Isotopic Labeling of Substrates (TAILS), comprising labeling and enrichment of protein N-termini, high-resolution mass spectrometry and bioinformatics. Cartilage was digested with ADAMTS5, MMP13 and CMA1, and TAILS was used to identify their specific activities. Results: Analysis of matched knee OA cartilage and synovial fluid degradomes consistently demonstrated cartilage breakdown products in synovial fluid. Of over 20,000 cleaved peptides in the OA cartilage and synovial fluid degradomes, 677, originating from 153 proteins, were present in all samples, the majority arising from cartilage. ADAMTS5, MMP13 and CMA1 digestion of cartilage identified numerous cleavage sites for each protease, distinct cleavage site preferences, and peptides arising from the activities of these proteases in synovial fluid. Conclusions: Cartilage ECM-derived proteolytic fragments are consistently present in synovial fluid, many attributable to ADAMTS5, MMP13 and CMA1 activity, which showed little overlap with each other or the previously determined HtrA1activity profile. The present work increases the proteolytic biomarker space for OA investigation, showing that diverse proteases contribute to cartilage destruction, and that their individual contributions can be determined using multiple protease-specific biomarkers.

2025-02-04 | PXD048053 | Pride

Synovial fluid proteomics from serial aspiration of ACL injured knees identifies candidate biomarkers for osteoarthritis

Project description:Patients with anterior cruciate ligament (ACL) tears have a significantly increased risk for developing knee osteoarthritis. These injuries often result in a knee effusion in response to the injury. Early changes in these effusions could be informative regarding initial steps in the development of post traumatic osteoarthritis. The purpose of this study was to test the hypothesis that the proteomics of knee synovial fluid changes over time following ACL injury.

2022-06-23 | MSV000089716 | MassIVE

Synovial fluid proteome changes in ACL injury-induced posttraumatic osteoarthritis: proteomics analysis of porcine knee synovial fluid

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2019-02-16 | PXD012720 | Pride

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