Show simple item record

Changes in serum and synovial fluid biomarkers after acute injury (NCT00332254).

dc.contributor.author Catterall, JB
dc.contributor.author Flannery, CR
dc.contributor.author Kraus, Virginia Byers
dc.contributor.author Stabler, Thomas
dc.coverage.spatial England
dc.date.accessioned 2015-11-10T22:47:51Z
dc.date.issued 2010
dc.identifier http://www.ncbi.nlm.nih.gov/pubmed/21194441
dc.identifier ar3216
dc.identifier.uri https://hdl.handle.net/10161/10881
dc.description.abstract INTRODUCTION: Acute trauma involving the anterior cruciate ligament is believed to be a major risk factor for the development of post-traumatic osteoarthritis 10 to 20 years post-injury. In this study, to better understand the early biological changes which occur after acute injury, we investigated synovial fluid and serum biomarkers. METHODS: We collected serum from 11 patients without pre-existing osteoarthritis from a pilot intervention trial (5 placebo and 6 drug treated) using an intra-articular interleukin-1 receptor antagonist (IL-1Ra) therapy, 9 of which also supplied matched synovial fluid samples at presentation to the clinic after acute knee injury (mean 15.2 ± 7.2 days) and at the follow-up visit for reconstructive surgery (mean 47.6 ± 12.4 days). To exclude patients with pre-existing osteoarthritis (OA), the study was limited to individuals younger than 40 years of age (mean 23 ± 3.5) with no prior history of joint symptoms or trauma. We profiled a total of 21 biomarkers; 20 biomarkers in synovial fluid and 13 in serum with 12 biomarkers measured in both fluids. Biomarkers analyzed in this study were found to be independent of treatment (P > 0.05) as measured by Mann-Whitney and two-way ANOVA. RESULTS: We observed significant decreases in synovial fluid (sf) biomarker concentrations from baseline to follow-up for (sf)C-Reactive protein (CRP) (P = 0.039), (sf)lubricin (P = 0.008) and the proteoglycan biomarkers: (sf)Glycosaminoglycan (GAG) (P = 0.019), and (sf)Alanine-Arginine-Glycine-Serine (ARGS) aggrecan (P = 0.004). In contrast, we observed significant increases in the collagen biomarkers: (sf)C-terminal crosslinked telopeptide type II collagen (CTxII) (P = 0.012), (sf)C1,2C (P = 0.039), (sf)C-terminal crosslinked telopeptide type I collagen (CTxI) (P = 0.004), and (sf)N-terminal telopeptides of type I collagen (NTx) (P = 0.008). The concentrations of seven biomarkers were significantly higher in synovial fluid than serum suggesting release from the signal knee: IL-1β (P < 0.0001), fetal aggrecan FA846 (P = 0.0001), CTxI (P = 0.0002), NTx (P = 0.012), osteocalcin (P = 0.012), Cartilage oligomeric matrix protein (COMP) (P = 0.0001) and matrix metalloproteinase (MMP)-3 (P = 0.0001). For these seven biomarkers we found significant correlations between the serum and synovial fluid concentrations for only CTxI (P = 0.0002), NTx (P < 0.0001), osteocalcin (P = 0.0002) and MMP-3 (P = 0.038). CONCLUSIONS: These data strongly suggest that the biology after acute injury reflects that seen in cartilage explant models stimulated with pro-inflammatory cytokines, which are characterized by an initial wave of proteoglycan loss followed by subsequent collagen loss. As the rise of collagen biomarkers in synovial fluid occurs within the first month after injury, and as collagen loss is thought to be irreversible, very early treatment with agents to either reduce inflammation and/or reduce collagen loss may have the potential to reduce the onset of future post-traumatic osteoarthritis. TRIAL REGISTRATION: The samples used in this study were derived from a clinical trial NCT00332254 registered with ClinicalTrial.gov.
dc.language eng
dc.relation.ispartof Arthritis Res Ther
dc.relation.isversionof 10.1186/ar3216
dc.subject Anti-Inflammatory Agents
dc.subject Biomarkers
dc.subject Collagen
dc.subject Double-Blind Method
dc.subject Enzyme-Linked Immunosorbent Assay
dc.subject Female
dc.subject Humans
dc.subject Inflammation
dc.subject Injections, Intra-Articular
dc.subject Interleukin 1 Receptor Antagonist Protein
dc.subject Knee Injuries
dc.subject Male
dc.subject Pilot Projects
dc.subject Proteoglycans
dc.subject Synovial Fluid
dc.subject Young Adult
dc.title Changes in serum and synovial fluid biomarkers after acute injury (NCT00332254).
dc.type Journal article
pubs.author-url http://www.ncbi.nlm.nih.gov/pubmed/21194441
pubs.begin-page R229
pubs.issue 6
pubs.organisational-group Clinical Science Departments
pubs.organisational-group Duke
pubs.organisational-group Duke Molecular Physiology Institute
pubs.organisational-group Institutes and Centers
pubs.organisational-group Medicine
pubs.organisational-group Medicine, Rheumatology and Immunology
pubs.organisational-group Orthopaedics
pubs.organisational-group Pathology
pubs.organisational-group School of Medicine
pubs.publication-status Published
pubs.volume 12
dc.identifier.eissn 1478-6362


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record