Post-translational aging of proteins in osteoarthritic cartilage and synovial fluid as measured by isomerized aspartate.
Abstract
INTRODUCTION: Aging proteins undergo non-enzymatic post-translational modification,
including isomerization and racemization. We hypothesized that cartilage with many
long-lived components could accumulate non-enzymatically modified amino acids in the
form of isomerized aspartate and that its liberation due to osteoarthritis (OA)-related
cartilage degradation could reflect OA severity. METHODS: Articular cartilage and
synovial fluid were obtained from 14 randomly selected total knee arthroplasty cases
(56 to 79 years old) and non-arthritis cartilage from 8 trauma cases (51 to 83 years
old). Paired lesional cartilage and non-lesioned OA cartilage were graded histologically
using a modified Mankin system. Paired cartilage and synovial fluids were assayed
for isomerized aspartate, phosphate-buffered saline/EDTA (ethylenediaminetetraacetic
acid) extractable glycosaminoglycans, and total protein. Macroscopically normal non-lesioned
OA cartilage was separated into superficial and deep regions when cartilage thickness
was at least 3 mm (n = 6). RESULTS: Normalized to cartilage wet weight, normal cartilage
and deep non-lesioned OA cartilage contained significantly (P < 0.05) more isomerized
aspartate than superficial non-lesioned OA cartilage and lesioned cartilage. Synovial
fluid isomerized aspartate correlated positively (R2 = 0.53, P = 0.02) and glycosaminoglycans
correlated negatively (R2 = 0.42, P = 0.04) with histological OA lesion severity.
Neither synovial fluid isomerized aspartate nor glycosaminoglycans nor total protein
correlated with histological scores of non-lesioned areas. CONCLUSIONS: We show for
the first time that human cartilage and synovial fluid contain measurable quantities
of an isomerized amino acid and that synovial fluid concentrations of isomerized aspartate
reflected severity of histological OA. Further assessment is warranted to identify
the cartilage proteins containing this modification and to assess the functional consequences
and biomarker applications of this analyte in OA.
Type
Journal articleSubject
AgedAged, 80 and over
Aspartic Acid
Biomarkers
Cartilage, Articular
Glycosaminoglycans
Humans
Isomerism
Middle Aged
Osteoarthritis, Knee
Protein Processing, Post-Translational
Proteins
Synovial Fluid
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https://hdl.handle.net/10161/10870Published Version (Please cite this version)
10.1186/ar2675Publication Info
Catterall, Jonathan B; Barr, Daniel; Bolognesi, Michael; Zura, Robert D; & Kraus,
Virginia B (2009). Post-translational aging of proteins in osteoarthritic cartilage and synovial fluid
as measured by isomerized aspartate. Arthritis Res Ther, 11(2). pp. R55. 10.1186/ar2675. Retrieved from https://hdl.handle.net/10161/10870.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
Michael Paul Bolognesi
Professor of Orthopaedic Surgery
As chief of the adult reconstruction service, the majority of my research effort has
been directed toward clinical outcomes, implant survivorship, functional recovery,
the biology of hip and knee arthritis and cost effectiveness.
Virginia Byers Kraus
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
Robert Douglas Zura
Associate Professor of Orthopaedic Surgery
This author no longer has a Scholars@Duke profile, so the information shown here reflects
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