title: Osteopontin ablation attenuates progression of colitis in TNBS model.
abstract: BACKGROUND
  OPN has been implicated in the inflammatory response to Crohn's disease. We hypothesized that OPN deficiency protects against different stages of TNBS-induced colitis in a modified model that mimics Crohn's disease.
  
  
  METHODS
  OPN-deficient and wildtype mice were treated intracolonically with TNBS and euthanized during acute, sub-acute and chronic colitis.
  
  
  RESULTS
  TNBS-treated wildtype mice developed severe colitis, but OPN-deficient mice were significantly protected. Wildtype mice showed significant infiltration of inflammatory cells including macrophages, and colonic transmural thickening that progressed to strictures, increased matrix collagen deposits (X2 fold), and granuloma formation. These pathological findings were partially attenuated by OPN deficiency. The inflammatory marker, serum amyloid A (SAA), markedly increased in sub-acute stages regardless of OPN status. Conversely, OPN deficiency significantly reduced concentration of SAA in the acute and chronic stages. Secretory OPN was upregulated particularly in acute stage in wildtypes (P < 0.001) and as expected not present in OPN-deficient animals. Flow cytometry analysis of splenic macrophages revealed significant increases in scavenger receptors, macrosialin and F4/80 markers' expression in wildtypes.
  
  
  CONCLUSIONS
  Our data support the role of OPN in induction of inflammation and establishment of chronic colitis. Therefore, OPN may represent a target for therapeutic intervention in Crohn's disease.
authors.affiliation: Department of Physiology, University of Kentucky Medical Center, Lexington, KY 40515-0298, USA. Hoz2@email.uky.edu
authors.forename: Helieh S
authors.initials: HS
authors.lastname: Oz
authors.forename: Jian
authors.initials: J
authors.lastname: Zhong
authors.forename: Willem J S
authors.initials: WJ
authors.lastname: de Villiers
mesh_terms: D000818:Animals; D001707:Biopsy, Needle; D003092:Colitis / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology*; D004195:Disease Models, Animal; D018450:Disease Progression; D005434:Flow Cytometry; D007150:Immunohistochemistry; D018836:Inflammation Mediators / Q000032:analysis / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053495:Osteopontin / Q000172:deficiency* / Q000378:metabolism; D011897:Random Allocation; D012016:Reference Values; D012680:Sensitivity and Specificity; D000685:Serum Amyloid A Protein / Q000032:analysis; D014302:Trinitrobenzenesulfonic Acid / Q000494:pharmacology*
chemical_list: D018836:Inflammation Mediators; D000685:Serum Amyloid A Protein; D053495:Osteopontin; D014302:Trinitrobenzenesulfonic Acid