title: Hypoxia appears at pre-arthritic stage and shows co-localization with early synovial inflammation in collagen induced arthritis.
abstract: OBJECTIVE
  The presence of hypoxia in rheumatoid synovium has been well known, but exact correlation between hypoxia and synovitis is unclear. The aim of our study was to investigate the time and spatial relationship and the correlation of severity between hypoxia and synovitis in pre-arthritic or early stage of inflammatory joint disease.
  
  
  METHODS
  DBA/1J mice were injected intradermally with type II collagen and adjuvant solution to induce arthritis; mice injected with only adjuvant were used as a control group. CIA and control mice were sacrificed weekly after the injection to evaluate serial pathological changes. H&E stain and hydroxyprobe-1 stain were performed to look at the status of inflammation and hypoxia.
  
  
  RESULTS
  In serial observations of tissue pathology, we could note the inflammation of synovium developing a week after the injection of type II collagen. Hypoxic change, measured by the hydroxyprobe-1 stain, was also identified in synovium as early as 1 week after the collagen injection, prior to clinically evident arthritis. In addition, we could observe that inflammation and hypoxia co-localize in the synovium and there was a positive correlation between the severity of hypoxia and the degree of synovitis.
  
  
  CONCLUSIONS
  Our results demonstrate that hypoxia takes place in synovium at the pre-arthritic stage of disease and have a close spatial relationship and a positive severity correlation with synovitis.
authors.affiliation: Department of Medicine, Soonchunhyang University College of Medicine, Bucheon, Korea.
authors.forename: C H
authors.initials: CH
authors.lastname: Jeon
authors.forename: J-K
authors.initials: JK
authors.lastname: Ahn
authors.forename: J-Y
authors.initials: JY
authors.lastname: Chai
authors.forename: H J
authors.initials: HJ
authors.lastname: Kim
authors.forename: E-K
authors.initials: EK
authors.lastname: Bae
authors.forename: S H
authors.initials: SH
authors.lastname: Park
authors.forename: E Y
authors.initials: EY
authors.lastname: Cho
authors.forename: H-S
authors.initials: HS
authors.lastname: Cha
authors.forename: K-S
authors.initials: KS
authors.lastname: Ahn
authors.forename: E-M
authors.initials: EM
authors.lastname: Koh
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental; D001172:Arthritis, Rheumatoid / Q000473:pathology / Q000503:physiopathology*; D000860:Hypoxia / Q000473:pathology / Q000503:physiopathology*; D051379:Mice; D013585:Synovitis / Q000473:pathology / Q000503:physiopathology*