title: Thrombin-cleaved osteopontin in synovial fluid of subjects with rheumatoid arthritis.
abstract: 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.
authors.affiliation: 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
authors.forename: Masahiro
authors.initials: M
authors.lastname: Hasegawa
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Nakoshi
authors.forename: Takahiro
authors.initials: T
authors.lastname: Iino
authors.forename: Akihiro
authors.initials: A
authors.lastname: Sudo
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Segawa
authors.forename: Masahiro
authors.initials: M
authors.lastname: Maeda
authors.forename: Toshimichi
authors.initials: T
authors.lastname: Yoshida
authors.forename: Atsumasa
authors.initials: A
authors.lastname: Uchida
mesh_terms: 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
chemical_list: D015415:Biomarkers; D053495:Osteopontin; D002097:C-Reactive Protein; D013917:Thrombin