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2018 ; 20
(1
): 131
Nephropedia Template TP
gab.com Text
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English Wikipedia
Glycation marker glucosepane increases with the progression of osteoarthritis and
correlates with morphological and functional changes of cartilage in vivo
#MMPMID29929535
Legrand C
; Ahmed U
; Anwar A
; Rajpoot K
; Pasha S
; Lambert C
; Davidson RK
; Clark IM
; Thornalley PJ
; Henrotin Y
; Rabbani N
Arthritis Res Ther
2018[Jun]; 20
(1
): 131
PMID29929535
show ga
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-1?-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-1?. 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-1? 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.