Thrombin-cleaved osteopontin levels in synovial fluid correlate with disease severity of knee osteoarthritis.
OBJECTIVE
although osteoarthritis (OA) is generally assessed using standard radiographic images in clinical practice, biochemical markers can be used to detect the disease and determine its severity. Osteopontin (OPN) is an extracellular matrix glycoprotein that is a potential inflammatory cytokine. Presence of the thrombin-cleaved form of OPN is well correlated with various inflammatory diseases. We examined whether thrombin-cleaved OPN in synovial fluid (SF) and synovium could be associated with the severity of knee OA.


METHODS
SF samples were obtained from 139 knees with OA. Thrombin-cleaved OPN product was determined using Western blotting. Levels of thrombin-cleaved and full-length OPN in SF were determined by ELISA. Synovium samples were analyzed by immunohistochemistry using an antibody specific to the thrombin-cleaved form.


RESULTS
western blotting showed the presence of thrombin-cleaved OPN in SF from patients with advanced OA. Concentrations of OPN full-length in OA knees were not statistically different from those in controls (p = 0.134). In contrast, levels of OPN N-half were significantly higher in OA knees than in controls (p = 0.042). Statistically significant correlation was found between thrombin-cleaved OPN and disease severity by Kellgren-Lawrence grade 1, 2, 3, and 4 (R = 0.274, p < 0.001). Immunohistochemistry of the synovium showed stronger reactivity in samples from subjects with advanced OA.


CONCLUSIONS
local generation of thrombin-cleaved OPN was increased with greater OA severity.
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
Masahiro
M
Hasegawa
Tatsuya
T
Segawa
Masahiro
M
Maeda
Toshimichi
T
Yoshida
Akihiro
A
Sudo
D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D015415:Biomarkers / Q000378:metabolism*; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020370:Osteoarthritis, Knee / Q000378:metabolism* / Q000473:pathology* / Q000503:physiopathology; D053495:Osteopontin / Q000378:metabolism*; D013582:Synovial Fluid / Q000737:chemistry*; D013917:Thrombin / Q000378:metabolism*
D015415:Biomarkers; D053495:Osteopontin; D013917:Thrombin