Changes in serum and synovial fluid biomarkers after acute injury (NCT00332254).
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.
Type
Journal articleSubject
Anti-Inflammatory AgentsBiomarkers
Collagen
Double-Blind Method
Enzyme-Linked Immunosorbent Assay
Female
Humans
Inflammation
Injections, Intra-Articular
Interleukin 1 Receptor Antagonist Protein
Knee Injuries
Male
Pilot Projects
Proteoglycans
Synovial Fluid
Young Adult
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https://hdl.handle.net/10161/10881Published Version (Please cite this version)
10.1186/ar3216Publication Info
Catterall, Jonathan B; Stabler, Thomas V; Flannery, Carl R; & Kraus, Virginia B (2010). Changes in serum and synovial fluid biomarkers after acute injury (NCT00332254). Arthritis Res Ther, 12(6). pp. R229. 10.1186/ar3216. Retrieved from https://hdl.handle.net/10161/10881.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Show full item recordScholars@Duke
Virginia Byers Kraus
Mary Bernheim Distinguished Professor of Medicine
My special area of expertise is as a clinician scientist investigating osteoarthritis.
Osteoarthritis is the most common form of joint disease in man and its incidence increases
with age. It is a problem of increasing concern to the medical community due to the
increasing longevity of the population. Trained as a molecular biologist and a Rheumatologist,
I endeavor to study this disease from bedside to bench. The work in this laboratory
focuses on osteoarthritis and deals w

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