title: Cadherin-11 involves in synovitis and increases the migratory and invasive capacity of fibroblast-like synoviocytes of osteoarthritis.
abstract: OBJECTIVE
  To detect the expression of cadherin-11 and its correlation with synovitis in osteoarthritis (OA), to explore the mechanism of over expression of cadherin-11 and its role in migratory or invasive capacity of fibroblast-like synoviocytes (FLS).
  
  
  METHODS
  Synovitis severity was recorded according to Krenn's scoring system in 25 osteoarthritis patients undergoing total knee arthroplasty. Cadherin-11 expression in OA synoviums and its correlation with synovitis score and systemic inflammation markers were explored. After induction with Interleukin-1 beta (IL-1β) or tumor necrosis factor-alpha (TNF-α),cadherin-11 expression on OA FLS was assessed by qPCR and western blot,the capacity of migration and invasion of OA FLS was tested by transwell assay, and matrix metalloproteinase-2 production was assessed with ELISA as cadherin-11 expression was up regulated after infection with cadherin-11 cDNA-containing lentivirus, also when cadherin-11 expression was knocked down after infection with cadherin 11 shRNA containing lentivirus.
  
  
  RESULTS
  Cadherin-11 expression in OA synovium showed significant differences among different grades of synovitis. Cadherin-11 in the lining layer was positively correlated with hyperplasia of the lining layer, density of the resident cells, inflammatory infiltrate, total synovitis score and D-dimer. Cadherin-11 in the sublining layer was positively correlated with the density of the resident cells, inflammatory infiltrate, total synovitis score and erythrocyte sedimentation rate. IL-1β or TNF-α could up-regulate cadherin-11 expression on OA FLS at transcriptional and protein level. Over expression of cadherin-11 increased migratory or invasive capacity of OA FLS, while cadherin-11 knock down reduced migratory or invasive capacity and MMP-2 production in OA FLS.
  
  
  CONCLUSIONS
  The over expression of cadherin-11 in osteoarthritis is positively correlated with synovitis severity, and can be driven by proinflammatory cytokines on OA FLS; cadherin-11 increases migratory or invasive capacity and MMP-2 production of fibroblast-like synoviocytes of osteoarthritis.
authors.affiliation: Arthritis Clinic and Research Center, People's Hospital, Peking University, Beijing China.
authors.forename: Xiaoquan
authors.initials: X
authors.lastname: Ding
authors.affiliation: Clinical Institute of Molecular Biology, People's Hospital, Peking University, Beijing China.
authors.forename: Yujun
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Arthritis Clinic and Research Center, People's Hospital, Peking University, Beijing China.
authors.forename: Yuelong
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Arthritis Clinic and Research Center, People's Hospital, Peking University, Beijing China.
authors.forename: Songyang
authors.initials: S
authors.lastname: Liu
authors.affiliation: Arthritis Clinic and Research Center, People's Hospital, Peking University, Beijing China.
authors.forename: Houshan
authors.initials: H
authors.lastname: Lu
authors.affiliation: Arthritis Clinic and Research Center, People's Hospital, Peking University, Beijing China. Electronic address: tiezheng_sun@163.com.
authors.forename: Tiezheng
authors.initials: T
authors.lastname: Sun
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000032:analysis; D015820:Cadherins / Q000276:immunology*; D018929:Cell Culture Techniques; D002465:Cell Movement / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000032:analysis; D005260:Female; D005347:Fibroblasts / Q000276:immunology* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D020370:Osteoarthritis, Knee / Q000276:immunology* / Q000473:pathology; D013583:Synovial Membrane / Q000276:immunology* / Q000473:pathology; D013585:Synovitis / Q000276:immunology* / Q000473:pathology
chemical_list: D015415:Biomarkers; D015820:Cadherins; D016207:Cytokines; C086960:osteoblast cadherin
keywords: Cadherin-11; Interleukin-1 beta; Osteoarthritis; Synovitis; Tumor necrosis factor-alpha