Best Oral Presentations (OP01–OP12)
i15
AUTHOR ABSTRACTS
BEST ORAL PRESENTATIONS
(OP01–OP12)
OP01. ATHEROSCLEROSIS IN ANKYLOSING
SPONYLITIS: THE RELATION WITH
METHYLENETETRAHYDROFOLATEREDUCTASE (C677T) GENE
POLYMORPHISIM AND PLASMA HOMOCYSTEINE LEVELS
Muharrem Geçene1, Figen Tuncay1, Pınar Borman1, Doğan Yücel2,
Mehmet S° enes2 and Bedriye KaniyeYılmaz3
1
Ankara Training and Research Hospital 1st Clinic of Physical Medicine
and Rehabilitation, Ankara, Turkey, 2Ankara Training and Research
Hospital Clinic of Biochemistry, Ankara, Turkey, 3Ankara Training and
Research Hospital Department of Radiology, Ankara, Turkey
Background: The aim of this study was to determine the intima-media
thickness (IMT) as an indicator of subclinical atherosclerosis in carotid
arteries and to assess the relation of these values with homocystein
levels and Methylenetetrahydrofolate reductase (MTHFR) C677T gene
polymorphism in patients with AS.
Methods: Fifty male AS patients and 50 controls were included in
the study. Serum lipids, vitamin B12, folic acid, homocystein and
acute phase protein levels were measured in all cases. A plasma
homocystein level of > 17 mmol/L was considered as hyperhomocysteinemia. MTHFR C677T gene polymorphisms were determined and
IMT of main carotid artery were evaluated ultrasonographically in all
subjects. BASDAI, ASDAS and BASMI were used to assess disease
activity and spinal mobility. The relationship between plasma homocystein level, MTHFR C677T gene polymorphism, IMT values and
clinical characteristics were determined.
Results: Fifty AS patients (mean age of 36.6 4.79 years) and 50 control
subjects (36.34 4.72 years) were included to the study. Demographic
characteristic were smiliar between the groups. Plasma homocystein
levels of AS patients and control group were also smiliar (14.26 9.96 vs
11.81 5.53 mmol/L). Hyperhomocysteinemia was present in 11 subjects in patient group (%22.0), while it was seen in 5 subjects in the
control group (%10.0), and MTHFR C677T genotype distribution
was CC 31 (%62), CT 14 (%28), TT 5 (%10) in AS patients and CC 26
(%52), CT 22 (%44), TT 2 (%4) in the control group, with no significant
difference between groups (p ¼ 0.102, p ¼ 0.174) and the mean carotid
IMT values were found to be similar between the groups. No relation was
found between plasma homocystein levels and clinical and demographical properties. The most important factor influencing homocystein
level was found as MTHFR 677TT genotype, which was established
to increase the risk of hyperhomocyteinemia risk by 11.308 fold.
Conclusions: In the present study, carotid IMT values, indicating
subclinical atherosclerosis, were found to be similar in AS and control
groups. The increase in the risk of atherosclerosis in AS patients
seems not be different from healthy subjects.
Disclosure statement: None.
OP02. ADENOSINE MODULATION OF THE PRO-FIBROGENIC
CYTOKINE IL-13 OCCURS VIA THE A2A ADENOSINE RECEPTOR
Lisa Franks, Ross Radusky, Jessica Feig, Patricia Fernandez,
Bruce Cronstein and Edwin Chan
New York University School of Medicine, New York, NY, USA.
Background: Our prior observations showed that the nucleoside
adenosine and its receptor mediate collagen production and dermal
fibrosis by human dermal fibroblasts in vitro. In addition, we showed
that IL-13 expression is upregulated in tissues characterized by high
levels of adenosine in the adenosine deaminase-deficient mouse
model. This suggests adenosine upregulates the pro-fibrogenic
cytokine IL-13. However, the receptor(s) and mechanism involved in
this upregulation remained unknown. The aim of this study was to
characterize further the contributions of endogenous adenosine and
adenosine A2A receptors to skin fibrosis.
Methods: In an in vitro study of cultured normal human dermal
fibroblasts, the effect of adenosine A2A receptor modulation on IL-13
expression was studied. Using both the A2A receptor agonist
(CGS21680, 1mM) and antagonist (ZM241385, 1mM), levels of IL-13
and IL-13 receptors were tested. Measurements of mRNA for IL-13
and three IL-13 receptor proteins, IL-13Ra1, IL-13Ra2 and IL-4 were
assessed using real-time PCR amplification.
Results: The A2A agonist induced elevated expression of message
for IL-13 and two of three IL-13 receptors: IL-13Ra1 and IL-13Ra2. A 5fold increase in expression was found for IL-13Ra1 and a more modest
1.8-fold increase in IL-13Ra2. These inducible elevations were blocked
by coincubation with the A2A receptor antagonist but not by antagonists
to other adenosine receptors. Incubation with the A2A receptor
antagonist alone did not affect the expression of IL-13 or its receptors.
Conclusion: Despite efforts at investigating the mechanisms underlying fibrogenic processes in the skin of patients with scleroderma, no
effective antifibrotic therapy exists. The nucleoside adenosine induces
expression of pro-fibrotic cytokine IL-13 and particularly its cognate
receptor IL-13Ra1.These findings suggest that blockade of the A2A
receptor may be useful as a novel therapeutic agent to modify dermal
fibrosis in scleroderma.
Disclosure: E.C. & B.C. hold a patent on the use of A2A antagonists in
fibrosis.
OP03. THE ROLE OF STROMAL CELL-DERIVED FACTOR-1
IN ENDOCHONDRAL OSSIFICATION AND PATHOGENESIS
OF OSTEOARTHRITIS
Gunwoo Kim1,2,3, Seungwoo Han1,2, Yeonkwan Jung2,
Shirine E Usmani3, Veronica Ulici3 and Frank Beier3
1
Division of Rheumatology, Department of Internal Medicine,
Daegu Fatima Hospital, Daegu, South Korea, 2Laboratory for arthritis
and bone biology, Fatima research institute, Daegu Fatima Hospital,
Daegu, South Korea, 3CIHR Group in Skeletal Development and
Remodeling, Department of Physiology and Pharmacology,
University of Western Ontario, London, Ontario, Canada
Background: Changes of endochondral ossification in the articular
cartilage, such as chondrocyte proliferation, differentiation and apoptosis, are thought to play an important role in the development of
osteoarthritis. Understanding the molecular mechanisms controlling the
endochondral ossification thus is important to understanding the pathogenesis of osteoarthritis. SDF-1a and aberrant endochondral ossification have been implicated in the pathogenesis of osteoarthritis, but how
these processes are connected is unclear. In this study, we investigated
the roles of SDF-1a on the endochondral ossification in mice.
Methods: Primary chondrocytes and tibial explants from embryonic
15.5 day-old mice were cultured with SDF-1a to assess the roles of
SDF-1a on the endochondral ossification. Total RNA was isolated from
primary cell cultures using a Qiagen RNeasy Mini Kit. Real-time PCR
analysis was performed using Applied Biosystems 7900 HT Real-Time
PCR System and TaqManÕ Gene Expression Assays. Organ culture
tissues were stained with safranin O/fast green and alcian blue/alizarin
red, and the immunohistochemistry was also performed.
Results: In primary chondrocyte cultures, the expression of chondrocyte proliferation marker, aggrecan, was increased, and the (...truncated)
