Thrombin-cleaved osteopontin in synovial fluid of subjects with rheumatoid arthritis.
OBJECTIVE
Osteopontin (OPN) is an extracellular matrix glycoprotein that has been recognized as a potential inflammatory cytokine. The function of OPN is modulated by protease digestion, and a thrombin-cleaved form of OPN is involved in the pathogenesis of various inflammatory disorders. We examined thrombin-cleaved OPN products in synovial fluid from patients with rheumatoid arthritis (RA) and osteoarthritis (OA).


METHODS
Synovial fluid samples were obtained from knees of 20 patients with RA and 111 patients with OA. Thrombin-cleaved OPN product was determined using Western blotting. Levels of thrombin- cleaved and full-length OPN in synovial fluid were determined by ELISA. Synovia were analyzed by immunohistochemistry using an antibody specific to the thrombin-cleaved form.


RESULTS
Immunoblotting showed the presence of thrombin-cleaved OPN in synovial fluid from patients with RA and OA. ELISA results showed no difference between concentrations of full-length OPN in the synovial fluid of RA and OA patients; however, thrombin-cleaved OPN concentrations in RA synovial fluid samples were roughly 30-fold higher compared with OA samples (p < 0.001). Synovial fluid concentrations of thrombin-cleaved OPN in RA did not correlate with C-reactive protein levels. Immunohistochemistry of the synovium showed stronger reactivity in RA than in OA samples.


CONCLUSIONS
Local generation of thrombin-cleaved OPN was increased in RA joints. Thrombin-cleaved OPN may be a useful biochemical marker of RA.
Hasegawa
Masahiro
M
Department of Orthopaedic Surgery, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu City, Mie 514-8507, Japan. masahase@clin.medic.mie-u.ac.jp
Nakoshi
Yutaka
Y
Iino
Takahiro
T
Sudo
Akihiro
A
Segawa
Tatsuya
T
Maeda
Masahiro
M
Yoshida
Toshimichi
T
Uchida
Atsumasa
A
D000368:Aged; D001172:Arthritis, Rheumatoid / Q000175:diagnosis* / Q000378:metabolism* / Q000503:physiopathology; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D015153:Blotting, Western; D002097:C-Reactive Protein / Q000032:analysis / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007596:Joints / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D053495:Osteopontin / Q000032:analysis / Q000378:metabolism*; D013582:Synovial Fluid / Q000378:metabolism*; D013917:Thrombin / Q000378:metabolism; D015854:Up-Regulation / Q000502:physiology
D015415:Biomarkers; D053495:Osteopontin; D002097:C-Reactive Protein; D013917:Thrombin