Giménez, P.

Horga, J.F.

Martínez, H.

Montell, E.

Peiró, A.M.

Simón-Talero, M.

Vergés, J.

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S200 Poster Presentations
381
NEGATIVE REGULATION OF GENE EXPRESSION OF
CARTILAGE DEGRADING GLYCOSIDASES IN HUMAN
OSTEOARTHRITIS AND RHEUMATOID ARTHRITIS
SYNOVIAL FIBROBLASTS
M. Pásztói1, K. Wellinger2, G. Nagy3, P. Géher3, T. Lakatos3,
P. Pócza1, B. György1, M. Holub1, Á. Kittel4, K. Pálóczy1,
M. Mazán1, A. Falus1, E. Buzás1, K. Tóth2
1Dept. of Genetics, Cell and Immunobiology, Semmelweis Univ.,
Budapest, Hungary; 2Univ. of Szeged, Szeged, Hungary; 3Dept.
of Rheumatology, Semmelweis Univ., Budapest, Hungary; 4Lab.
of Molecular Pharmacology, Inst. of Experimental Med.,
Hungarian Academy of Sci., Budapest, Hungary
Purpose: We have shown earlier that exoglycosidases alone or
in combination with matrix metalloproteinases, are capable of
degrading the extracellular matrix of hyaline cartilage. While it is
well established that the expression of matrix metalloproteinases
is upregulated under certain conditions, there is no information
concerning the regulation of cartilage degrading glycosidases.
Objective: The lack of information in this ﬁeld has compelled us
to carry out a systemic study to characterize gene expression
regulation in synovial ﬁbroblasts of patients with osteoarthritis and
rheumatoid arthritis.
Methods: We tested the gene expression of β-D-hexosaminidase,
β-D-glucuronidase, hyaluronidase, sperm adhesion molecule1 and
klotho in synovial ﬁbroblasts, synovial ﬂuid and synovial membrane
samples of patients with osteoarthritis and rheumatoid arthritis.
Results: We could detect the expression of β-D-hexosaminidase,
β-D-glucuronidase, hyaluronidase, and klotho in synovial mem-
brane samples, hexosaminidase being the major glycosidase ex-
pressed within the joints. We found that the gene expression of
cartilage degrading glycosidases was moderately downregulated
by proinﬂammatory cytokines including TNF-alpha, IL-1beta and
IL-17. TGF-beta profoundly downregulated the expression of gly-
cosidases in synovial ﬁbroblasts derived from either osteoarthritis
or rheumatoid arthritis patients.
Conclusions: These data suggest that gene expression of syn-
ovial ﬁbroblast glycosidases does not differ signiﬁcantly in patients
with OA and RA, and it is under negative regulation by some
locally expressed cytokines.
382
FUNCTIONAL BETA-2-ADRENERGIC RECEPTOR STATUS
COULD INFLUENCE THE INFLAMMATORY RESPONSE IN
ARTHROSIC PATIENTS
J.F. Horga1, A.M. Peiró1, M. Simón-Talero2, P. Giménez3,
H. Martínez4, E. Montell4, J. Vergés4
1Clinical Pharmacology Div. Hosp. Gen. de Alicante, Alicante,
Spain; 2C.S La Florida, Alicante, Spain; 3CIBERehd, Inst. de
Salud Carlos III, Madrid, Spain; 4Clinical Res. Unit. Scientiﬁc Med.
Dept. BIOIBÉRICA, S.A., Barcelona, Spain
Purpose: The beta-2-adrenergic receptor (ADRB2) represents
a junction between sympathetic nervous system and immune
system. In fact, inﬂammatory articular illnesses are associated to
a lower number of ADRB2 in PBMC which can be correlated to
a decrease of cell immune functionality and clinical evolution. We
want to ﬁnd the relation between ADRB2 haplotype in arthrosic
patients and the response to adrenergic stimulation through cyclic
AMP (cAMP) production.
Methods: In total, 30 arthrosic patients (mean age= 70 years; sex
(M/F) 10/20) and 20 healthy controls were included (mean age=
71 years; sex (M/F) 12/8). We determinate: a) Lymphocyte cAMP
production before and after isoproterenol (ISO, from 10-8 to 10-3)
stimulation in vitro; b) Allelic forms of amino acid 16, 27 and 164
from ADBR2 gen in DNA-leukocyt. Also, patient’s clinical data was
registered.
Results: Signiﬁcant decreases were found in AMPc (pmol/mL) in
arthrosic patients vs. controls (mean values at ISO 10-8 were: 14
vs. 20 pmol/mL; at ISO 10-4 were: 41 vs. 78 pmol/mL, p<0.05) (Fig.
1). In arthrosic patients, although ADRB2 response was lower, we
did not found a functional inﬂuence of these polymorphisms on
cAMP level because presence of allelic variants was similar in
both groups.
Figure 1. Cyclic AMP level under different isoproterenol concentration stimulus
from 10-3 to 10-9.
Conclusions: It seems that functional ADRB2 status is a fac-
tor that could inﬂuence the inﬂammatory response in arthrosic
patients.
Imaging
383
KNEE JOINT SHAPE ASSESSED BY ACTIVE SHAPE
MODELLING OF PLAIN RADIOGRAPHS IS RELATED TO
OSTEOARTHRITIS SEVERITY
R.J. Barr1, J.S. Gregory1, K. Yoshida1, S. Alesci2, D.M. Reid1,
R.M. Aspden1
1Univ. of Aberdeen, Aberdeen, United Kingdom; 2Discovery
Translational Med., Wyeth Res., Collegeville, PA
Purpose: The use of plain radiographs for the assessment of
Osteoarthritis (OA) is well established. In a recent study, we
demonstrated that Active Shape Modelling (ASM) of the hip joint,
measured on radiographs, can quantify the severity of hip OA and
may be able to predict the risk of rapid OA progression. ASM
describes the shape of the joint in an image in terms of “modes
of variation”, which are assigned scores describing how many
standard deviations each mode lies from the mean mode score of
all the images used in the modelling.
The aim of this study was to determine whether a knee ASM could
be developed for knee radiographs to assess the relationship
between shape and OA severity, assessed by Kellgren-Lawrence
grade (KLG).
Methods: 107 subjects were recruited using the local Radiology
Information System. All subjects had undergone bilateral knee
radiographs in the previous 12 months. Each knee was assigned
a KLG. The cohort encompassed the full spectrum of KLG (0-4).
A new 85 point model template was developed using the ASM
toolkit (Manchester University, Manchester, UK) and applied to
digitized knee radiographs. The model included the femur, tibia,
femoral and tibial osteophytes, tibial plateau, femoral condyles and
intercondylar notch (Figure 1). Pearson correlation analysis was
used to test the relationship between mode scores and KLG.


382 FUNCTIONAL BETA-2-ADRENERGIC RECEPTOR STATUS COULD INFLUENCE THE INFLAMMATORY RESPONSE IN ARTHROSIC PATIENTS 

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382 FUNCTIONAL BETA-2-ADRENERGIC RECEPTOR STATUS COULD INFLUENCE THE INFLAMMATORY RESPONSE IN ARTHROSIC PATIENTS

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