title: Inhibition of furin results in increased growth, invasiveness and cytokine production of synoviocytes from patients with rheumatoid arthritis.
abstract: OBJECTIVE
  Fibroblast-like synoviocytes derived from patients with rheumatoid arthritis play a key role by local production of cytokines and proteolytic enzymes that degrade the extracellular matrix and cartilage. These synoviocytes acquire phenotypic characteristics commonly observed in transformed cells, like anchorage-independent growth, increased proliferation and invasiveness, and insensitivity to apoptosis. Furin is a ubiquitous proprotein convertase that is capable of cleaving precursors of a wide variety of proteins. In patients with rheumatoid arthritis, furin is reported to be highly expressed in the synovial pannus compared with healthy persons. However, the mechanisms are poorly understood. This study is to explore the effect of furin overexpression in rheumatoid synoviocytes.
  
  
  METHODS
  In this study, RNA interference was used to knock down furin expression and to assess the resultant effects on biological behaviors of synoviocytes, such as cell proliferation, invasion, migration, cell cycle and cell apoptosis. In addition, the production of inflammatory cytokines was evaluated.
  
  
  RESULTS
  The results showed that the inhibition of furin enhanced proliferation, invasion, and migration of synoviocytes in vitro. Cell cycle was accelerated and cell death was affected by furin knockdown. Also, the inhibition of furin increased interleukin-1β and tumor necrosis factor-α secretion of synoviocytes.
  
  
  CONCLUSIONS
  Inhibition of furin enhances invasive phenotype of synoviocytes from patients with rheumatoid arthritis, implying a protective role of furin. Agents targeting upregulation of furin may have therapeutic potential for rheumatoid arthritis.
authors.affiliation: Department of Bone and Joint Surgery, Shandong Provincial Hospital affiliated to Shandong University, Shandong University, Jinan, Shandong 250021, PR China.
authors.forename: Changshun
authors.initials: C
authors.lastname: Wu
authors.affiliation: Department of Bone and Joint Surgery, Shandong Provincial Hospital affiliated to Shandong University, Shandong University, Jinan, Shandong 250021, PR China.
authors.forename: Zezhong
authors.initials: Z
authors.lastname: Song
authors.affiliation: Cancer Center, Shandong Provincial Hospital affiliated to Shandong University, Shandong University, Jinan, Shandong 250021, PR China.
authors.forename: Huiling
authors.initials: H
authors.lastname: Liu
authors.affiliation: Shandong Medicinal and Biotechnology Center, Shandong Academy of Medical Sciences, Jinan, Shandong 250062, PR China.
authors.forename: Jihong
authors.initials: J
authors.lastname: Pan
authors.affiliation: Shandong Medicinal and Biotechnology Center, Shandong Academy of Medical Sciences, Jinan, Shandong 250062, PR China.
authors.forename: Huiyu
authors.initials: H
authors.lastname: Jiang
authors.affiliation: Department of Oral and Maxillofacial Surgery, Shandong Provincial Hospital affiliated to Shandong University, Shandong University, Jinan, Shandong 250021, PR China.
authors.forename: Chao
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Bone and Joint Surgery, Shandong Provincial Hospital affiliated to Shandong University, Shandong University, Jinan, Shandong 250021, PR China.
authors.forename: Zexing
authors.initials: Z
authors.lastname: Yan
authors.affiliation: Cancer Center, Shandong Provincial Hospital affiliated to Shandong University, Shandong University, Jinan, Shandong 250021, PR China. Electronic address: hongfeng1268@126.com.
authors.forename: Hong
authors.initials: H
authors.lastname: Feng
authors.affiliation: Department of Bone and Joint Surgery, Shandong Provincial Hospital affiliated to Shandong University, Shandong University, Jinan, Shandong 250021, PR China.
authors.forename: Shui
authors.initials: S
authors.lastname: Sun
mesh_terms: D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000473:pathology; D002465:Cell Movement / Q000276:immunology; D049109:Cell Proliferation; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis*; D045683:Furin / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000276:immunology*; D006801:Humans; D013583:Synovial Membrane / Q000276:immunology* / Q000473:pathology; D000070918:Synoviocytes / Q000276:immunology* / Q000473:pathology
chemical_list: D016207:Cytokines; D045683:Furin
keywords: Fibroblast-like synoviocyte; Furin; Rheumatoid arthritis; Synovium