title: Tumor necrosis factor alpha drives cadherin 11 expression in rheumatoid inflammation.
abstract: OBJECTIVE
  Cadherin 11 expressed on fibroblast-like synoviocytes (FLS) plays a key role in normal synovial architecture. The purpose of this study was to examine the expression of cadherin 11 in human synovitis.
  
  
  METHODS
  Cadherin 11 expression in synovial biopsy samples from patients with various types of arthritis and in lung biopsy samples from patients with interstitial pneumonitis (IP) was examined by immunostaining. The regulation of cadherin 11 expression in human FLS was assessed by quantitative reverse transcription-polymerase chain reaction analysis and Western blotting. Therapeutic modulation of synovial cadherin 11 was assessed before and after effective antiinflammatory therapy.
  
  
  RESULTS
  Abundant staining for cadherin 11 was seen in the intimal lining layer and the synovial sublining in inflamed tissues, with discrete staining in noninflammatory osteoarthritic (OA) tissues. The pattern and degree of immunostaining were similar in tissues from patients with rheumatoid arthritis (RA), nonpsoriatic spondylarthritis (SpA), psoriatic arthritis (PsA), and inflammatory OA. Clear staining for cadherin 11 was also observed in lung tissues from RA-associated IP and idiopathic IP patients, but was very limited in normal lung tissue. Cadherin 11 staining correlated strongly with the degree of inflammatory infiltration of the tissue, as well as with the C-reactive protein level and the erythrocyte sedimentation rate in RA patients. In vitro, cadherin 11 expression by FLS was consistently up-regulated by tumor necrosis factor alpha (TNFalpha) at the protein, but not the messenger RNA, level. Cadherin 11 staining in vivo was strongly down-regulated by prednisone treatment in RA patients and by TNFalpha blockade in SpA patients.
  
  
  CONCLUSIONS
  Cadherin 11 expression is regulated by mediators of inflammation, such as TNFalpha. Since cadherin 11 plays an important role in cartilage destruction in experimental arthritis, down-modulation of cadherin 11 by potent antiinflammatory therapies in humans with arthritis may contribute to halting cartilage damage.
authors.affiliation: Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Bernard
authors.initials: B
authors.lastname: Vandooren
authors.forename: Tineke
authors.initials: T
authors.lastname: Cantaert
authors.forename: Mariëtte
authors.initials: M
authors.lastname: ter Borg
authors.forename: Troy
authors.initials: T
authors.lastname: Noordenbos
authors.forename: Rodger
authors.initials: R
authors.lastname: Kuhlman
authors.forename: Daniëlle
authors.initials: D
authors.lastname: Gerlag
authors.forename: Tim
authors.initials: T
authors.lastname: Bongartz
authors.forename: Kris
authors.initials: K
authors.lastname: Reedquist
authors.forename: Paul P
authors.initials: PP
authors.lastname: Tak
authors.forename: Dominique
authors.initials: D
authors.lastname: Baeten
mesh_terms: D000328:Adult; D000368:Aged; D018501:Antirheumatic Agents / Q000627:therapeutic use; D015820:Cadherins / Q000378:metabolism*; D015331:Cohort Studies; D005260:Female; D005347:Fibroblasts / Q000378:metabolism*; D006801:Humans; D008168:Lung / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D012216:Rheumatic Diseases / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D013583:Synovial Membrane / Q000378:metabolism* / Q000503:physiopathology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000276:immunology*
chemical_list: D018501:Antirheumatic Agents; D015820:Cadherins; D014409:Tumor Necrosis Factor-alpha; C086960:osteoblast cadherin