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Author Rabbani, Naila ♦ Legrand, Catherine ♦ Anwar, Attia ♦ Davidson, Rose K. ♦ Pasha, Sabah ♦ Clark, Ian M. ♦ Rajpoot, Kashif ♦ Ahmed, Usman ♦ Thornalley, Paul J. ♦ Lambert, Cécile ♦ Henrotin, Yves
Source Directory of Open Access Journals (DOAJ)
Content type Text
Publisher BioMed Central
File Format HTM / HTML
Date Created 2018-08-20
Copyright Year ©2018
Language English
Subject Domain (in LCC) RC925-935
Subject Keyword Glycation ♦ Inflammation ♦ Citrullination ♦ Internal medicine ♦ Medicine ♦ Diseases of the musculoskeletal system ♦ Machine learning ♦ Oxidative stress ♦ Specialties of internal medicine
Abstract Abstract Background Changes of serum concentrations of glycated, oxidized, and nitrated amino acids and hydroxyproline and anticyclic citrullinated peptide antibody status combined by machine learning techniques in algorithms have recently been found to provide improved diagnosis and typing of early-stage arthritis of the knee, including osteoarthritis (OA), in patients. The association of glycated, oxidized, and nitrated amino acids released from the joint with development and progression of knee OA is unknown. We studied this in an OA animal model as well as interleukin-1β-activated human chondrocytes in vitro and translated key findings to patients with OA. Methods Sixty male 3-week-old Dunkin-Hartley guinea pigs were studied. Separate groups of 12 animals were killed at age 4, 12, 20, 28 and 36 weeks, and histological severity of knee OA was evaluated, and cartilage rheological properties were assessed. Human chondrocytes cultured in multilayers were treated for 10 days with interleukin-1β. Human patients with early and advanced OA and healthy controls were recruited, blood samples were collected, and serum or plasma was prepared. Serum, plasma, and culture medium were analyzed for glycated, oxidized, and nitrated amino acids. Results Severity of OA increased progressively in guinea pigs with age. Glycated, oxidized, and nitrated amino acids were increased markedly at week 36, with glucosepane and dityrosine increasing progressively from weeks 20 and 28, respectively. Glucosepane correlated positively with OA histological severity (r = 0.58, p < 0.0001) and instantaneous modulus (r = 0.52–0.56; p < 0.0001), oxidation free adducts correlated positively with OA severity (p < 0.0009–0.0062), and hydroxyproline correlated positively with cartilage thickness (p < 0.0003–0.003). Interleukin-1β increased the release of glycated and nitrated amino acids from chondrocytes in vitro. In clinical translation, plasma glucosepane was increased 38% in early-stage OA (p < 0.05) and sixfold in patients with advanced OA (p < 0.001) compared with healthy controls. Conclusions These studies further advance the prospective role of glycated, oxidized, and nitrated amino acids as serum biomarkers in diagnostic algorithms for early-stage detection of OA and other arthritic disease. Plasma glucosepane, reported here for the first time to our knowledge, may improve early-stage diagnosis and progression of clinical OA.
ISSN 14786362
Age Range 18 to 22 years ♦ above 22 year
Educational Use Research
Education Level UG and PG ♦ Career/Technical Study
Learning Resource Type Article
Publisher Date 2018-06-01
e-ISSN 14786354
Journal Arthritis Research & Therapy
Volume Number 20
Issue Number 1
Page Count 16
Starting Page 1
Ending Page 16


Source: Directory of Open Access Journals (DOAJ)