Enhanced local production of osteopontin in rheumatoid joints.
OBJECTIVE
To investigate the involvement of osteopontin (OPN) in the pathogenesis of rheumatoid arthritis (RA), localization and production of OPN were examined in patients with RA.


METHODS
Localization of OPN in the rheumatoid synovium was examined by immunohistochemistry. In vitro OPN production by cultured synovial cells from patients with RA (n = 5) and with osteoarthritis (OA) (n = 5) was assessed by ELISA. OPN concentrations in plasma and synovium were quantified in patients with RA (n = 23) by 2 distinct ELISA systems to measure both thrombin cleaved and non-cleaved OPN. The same experiments were done in patients with OA (n = 15) and healthy volunteers (n = 10) as a control.


RESULTS
OPN was highly detected by immunohistochemistry predominantly in the RA synovial lining cells, while less and scattered OPN was detected in OA synovial tissues. ELISA revealed that cultured RA synovial cells secreted significantly more OPN than OA cells. ELISA also showed a marked increase of OPN levels in synovial fluid (SF) of patients with RA and with OA compared to the control plasma OPN levels, although OPN levels were not increased in RA and OA plasma compared to healthy controls. SF OPN levels of patients with RA were significantly higher than those of patients with OA, and correlated with serum C-reactive protein levels. The ratios of thrombin cleaved versus non-cleaved OPN were significantly increased in RA plasma and SF compared with OA plasma and SF and plasma from healthy controls.


CONCLUSIONS
Our results revealed enhanced local production of OPN in rheumatoid joints, suggesting involvement of OPN in the pathogenesis of RA.
Ohshima
Shiro
S
Department of Molecular Medicine, Osaka University Medical School, Osaka, Japan.
Yamaguchi
Norihiko
N
Nishioka
Katsuhiro
K
Mima
Toru
T
Ishii
Taeko
T
Umeshita-Sasai
Mitsuko
M
Kobayashi
Hideyuki
H
Shimizu
Masatoshi
M
Katada
Yoshinori
Y
Wakitani
Shigeyuki
S
Murata
Norikazu
N
Nomura
Shintaro
S
Matsuno
Hiroaki
H
Katayama
Rie
R
Kon
Shigeyuki
S
Inobe
Manabu
M
Uede
Toshimitsu
T
Kawase
Ichiro
I
Saeki
Yukihiko
Y
D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D002478:Cells, Cultured; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D010003:Osteoarthritis / Q000378:metabolism / Q000473:pathology; D053495:Osteopontin; D012795:Sialoglycoproteins / Q000276:immunology / Q000378:metabolism*; D013583:Synovial Membrane / Q000378:metabolism* / Q000473:pathology
C506895:SPP1 protein, human; D012795:Sialoglycoproteins; D053495:Osteopontin