title: The expression and pathophysiological role of osteopontin in Graves' disease.
abstract: BACKGROUND
  Graves' disease (GD) is a common autoimmune disease that affects the thyroid gland. Its pathogenesis is tightly involved with aberrant proinflammatory cytokine production. Osteopontin (OPN), an extracellular matrix protein of pleiotropic properties, has recently been recognized as a potent inflammatory cytokine in several autoimmune diseases.
  
  
  OBJECTIVE
  This study sought to explore the pathophysiological role of OPN in GD by comparing OPN levels in initial GD patients and healthy controls.
  
  
  METHODS
  Seventy-six patients who met criteria for initial GD and sixty-five healthy controls were recruited. OPN and other clinical GD diagnosis parameters were measured. In addition, the coexpression of several OPN receptors as well as various nuclear factor-κB (NF-κB) downstream target genes were examined in peripheral blood mononuclear cells from human subjects. The effect of OPN on NF-κB activation was determined by in vitro assays.
  
  
  RESULTS
  We demonstrated for the first time that the OPN levels are enhanced in serum from GD patients. OPN levels are strongly associated with clinical serum parameters for GD diagnosis. The coexpression of selective OPN receptors and inflammatory response genes was enhanced in peripheral blood mononuclear cells from GD patients. Furthermore, serum from GD patients activated NF-κB activity in vitro, which was significantly suppressed by OPN monoclonal antibody abrogation.
  
  
  CONCLUSIONS
  These data indicated a clinical correlation between serum OPN levels and GD. OPN could affect GD development through NF-κB activation and the subsequent changes in inflammatory milieu. OPN could serve as a novel biomarker for GD as well as a potential target for GD treatment.
authors: Laboratory of Endocrinology and Metabolism, Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200025, China.
authors: Lingyan
authors: L
authors: Xu
authors: Xinran
authors: X
authors: Ma
authors: Yanyan
authors: Y
authors: Wang
authors: Xiaoli
authors: X
authors: Li
authors: Yicheng
authors: Y
authors: Qi
authors: Bin
authors: B
authors: Cui
authors: Xiaoying
authors: X
authors: Li
authors: Guang
authors: G
authors: Ning
authors: Shu
authors: S
authors: Wang
mesh_terms: D000328:Adult; D005260:Female; D006111:Graves Disease / Q000097:blood*; D006801:Humans; D016898:Interferon-alpha / Q000097:blood; D007371:Interferon-gamma / Q000097:blood; D008875:Middle Aged; D053495:Osteopontin / Q000097:blood*
chemical_list: D016898:Interferon-alpha; D053495:Osteopontin; D007371:Interferon-gamma