 |
MR Vol.12 No.2 indexに戻る
 |
MODERN RHEUMATOLOGY
Vol.12 No.2 |
 |
|
|
 |
|
|
Comparison of the inhibitory effects of two types
(90 kDa and 190 kDa) of hyaluronic acid on the expression of fibrinolytic
factors in human synovial fibroblasts |
|
|
| T. Nonaka1, H. Kikuchi1, S. Sohen1, K.
Fukuda1, C. Hamanishi1, S. Tanaka1 |
| (1)Department of Orthopaedic Surgery, Kinki
University School of Medicine, 377-2 Ohnohigashi, Osakasayama 589-8511,
Japan |
| |
| Abstract |
| Abstract Hyaluronic acid (HA) has been shown
to be clinically effective, and is currently used for the treatment
of arthropathy. We previously reported that HA of molecular weight
90 kDa (90-HA) inhibits the fibrinolytic factors in human synovial
fibroblasts. In the present study, we investigated the effect of
high molecular weight (190 kDa) HA (190-HA) compared with 90-HA
on the pericellular fibrinolytic system of human synovial fibroblasts
in osteoarthritis (OA) and rheumatoid arthritis (RA). Human synovial
fibroblasts were obtained from synovial tissues of OA and RA, and
were cultured in the presence and absence of 90-HA and 190-HA.
Antigens of urokinase-type plasminogen activator (u-PA) and PA
inhibitor-1 (PAI-1) were measured by ELISA, and the u-PA activity
of the cell surface fraction was evaluated by electrophoretic enzymography.
The binding assay of u-PA and the immunocytochemical analysis of
u-PA were performed to detect u-PA receptor (u-PAR). HA inhibited
the secretion of both u-PA and PAI-1 antigens from the synovial
fibroblasts of OA to their conditioned medium, and the degree of
inhibition was more effective in OA than in RA. The u-RA binding
assay to these cells showed that both 90-HA and 190-HA slightly
decreased the maximal number of binding sites (Bmax) in OA. However,
in RA, stimulation with 90-HA and 190-HA decreased Bmax by a half
and a quarter, respectively. Immunohistochemical analysis showed
that u-PAR was constitutively expressed in both synovial fibroblasts,
but if these cells were treated with HA, the decrease in the staining
of u-PAR was more pronounced in RA than in OA. Furthermore, the
degree was more effective with 190-HA than with 90-HA. HA inhibited
the pericellular fibrinolytic activity mediated by the u-PA/u-PAR
system in synovial fibroblasts of OA and RA, and 190-HA inhibited
it more effectively than 90-HA |
| |
| Key words |
| Key words Hyaluronic acid (HA) ・ Rheumatoid
arthritis (RA) ・ Synovial fibroblasts ・ Urokinase-type plasminogen
activator receptor (u-PAR) |
|
|
 |
|
|
