title: ADAM-10 is overexpressed in rheumatoid arthritis synovial tissue and mediates angiogenesis.
abstract: OBJECTIVE
  To examine the expression of ADAM-10 in rheumatoid arthritis (RA) synovial tissue (ST) and the role it plays in angiogenesis.
  
  
  METHODS
  ADAM-10 expression was determined using immunohistology, Western blotting, and quantitative polymerase chain reaction. In order to examine the role of ADAM-10 in angiogenesis, we performed in vitro Matrigel tube formation and chemotaxis assays using human microvascular endothelial cells (HMVECs) transfected with control or ADAM-10 small interfering RNA (siRNA). To determine whether ADAM-10 plays a role in angiogenesis in the context of RA, we performed Matrigel assays using a coculture system of HMVECs and RA synovial fibroblasts.
  
  
  RESULTS
  Endothelial cells and lining cells within RA ST expressed high levels of ADAM-10 compared with cells within osteoarthritis ST and normal ST. ADAM-10 expression was significantly elevated at the protein and messenger RNA levels in HMVECs and RA synovial fibroblasts stimulated with proinflammatory mediators compared with unstimulated cells. ADAM-10 siRNA-treated HMVECs had decreased endothelial cell tube formation and migration compared with control siRNA-treated HMVECs. In addition, ADAM-10 siRNA-treated HMVECs from the RA synovial fibroblast coculture system had decreased endothelial cell tube formation compared with control siRNA-treated HMVECs.
  
  
  CONCLUSIONS
  These data show that ADAM-10 is overexpressed in RA and suggest that ADAM-10 may play a role in RA angiogenesis. ADAM-10 may be a potential therapeutic target in inflammatory angiogenic diseases such as RA.
authors.affiliation: University of Michigan Medical School, Ann Arbor, MI 48109-2200, USA.
authors.forename: Takeo
authors.initials: T
authors.lastname: Isozaki
authors.forename: Bradley J
authors.initials: BJ
authors.lastname: Rabquer
authors.forename: Jeffrey H
authors.initials: JH
authors.lastname: Ruth
authors.forename: G Kenneth
authors.initials: GK
authors.lastname: Haines
authors.forename: Alisa E
authors.initials: AE
authors.lastname: Koch
mesh_terms: D051722:ADAM Proteins / Q000378:metabolism*; D000072197:ADAM10 Protein; D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism*; D000818:Animals; D001172:Arthritis, Rheumatoid / Q000378:metabolism* / Q000503:physiopathology; D015153:Blotting, Western; D002478:Cells, Cultured; D003094:Collagen; D004338:Drug Combinations; D042783:Endothelial Cells / Q000378:metabolism* / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D005347:Fibroblasts; D006801:Humans; D007150:Immunohistochemistry; D007797:Laminin; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D009389:Neovascularization, Pathologic / Q000378:metabolism* / Q000473:pathology; D011509:Proteoglycans; D034622:RNA Interference; D060888:Real-Time Polymerase Chain Reaction; D013583:Synovial Membrane / Q000378:metabolism*
chemical_list: D004338:Drug Combinations; D007797:Laminin; D008565:Membrane Proteins; D011509:Proteoglycans; C059485:matrigel; D003094:Collagen; D053829:Amyloid Precursor Protein Secretases; D051722:ADAM Proteins; D000072197:ADAM10 Protein; C491236:ADAM10 protein, human