title: Small ubiquitin-like modifier 1 [corrected] mediates the resistance of prosthesis-loosening fibroblast-like synoviocytes against Fas-induced apoptosis.
abstract: OBJECTIVE
  To study the expression of small ubiquitin-like modifier 1 (SUMO-1) in aseptic loosening of prosthesis implants and to investigate its role in regulating the susceptibility of prosthesis-loosening fibroblast-like synoviocytes (FLS) to Fas-induced apoptosis.
  
  
  METHODS
  Specimens of aseptically loosened tissue were obtained at revision surgery, and the expression of SUMO-1 was analyzed by in situ hybridization. SUMO-1 levels in FLS were determined by quantitative polymerase chain reaction and Western blot analysis. Immunohistochemistry and confocal microscopy were used to study the subcellular localization of SUMO-1. The functional role of SUMO-1 in Fas-induced apoptosis of prosthesis-loosening FLS was investigated by small interfering RNA-mediated knockdown of SUMO-1 and by gene transfer of the nuclear SUMO-specific protease SENP1.
  
  
  RESULTS
  SUMO-1 was expressed strongly in aseptically loosened tissue and was found prominently at sites adjacent to bone. Prosthesis-loosening FLS expressed levels of SUMO-1 similar to the levels expressed by rheumatoid arthritis (RA) FLS, with SUMO-1 being found mainly in promyelocytic leukemia protein nuclear bodies. Knockdown of SUMO-1 had no effect on spontaneous apoptosis but significantly increased the susceptibility of prosthesis-loosening FLS to Fas-induced apoptosis. Gene transfer of the nuclear SUMO-specific protease SENP1 reverted the apoptosis-inhibiting effects of SUMO-1.
  
  
  CONCLUSIONS
  These data suggest that SUMO-1 is involved in the activation of both RA FLS and prosthesis-loosening FLS by preventing these cells from undergoing apoptosis. Modification of nuclear proteins by SUMO-1 contributes to the antiapoptotic effects of SUMO-1 in prosthesis-loosening FLS, providing evidence for the specific activation of sumoylation during their differentiation. Therefore, SUMO-1 may be an interesting target for novel strategies to prevent aseptic prosthesis loosening.
authors: University Hospital Muenster, Muenster, Germany.
authors: Ingmar
authors: I
authors: Meinecke
authors: Géza
authors: G
authors: Pap
authors: Heidi
authors: H
authors: Mendoza
authors: Steffen
authors: S
authors: Drange
authors: Stephan
authors: S
authors: Ender
authors: Simon
authors: S
authors: Strietholt
authors: Renate E
authors: RE
authors: Gay
authors: Christine
authors: C
authors: Seyfert
authors: Barbara
authors: B
authors: Ink
authors: Steffen
authors: S
authors: Gay
authors: Thomas
authors: T
authors: Pap
authors: Marvin A
authors: MA
authors: Peters
mesh_terms: D017209:Apoptosis / Q000502:physiology*; D001172:Arthritis, Rheumatoid / Q000378:metabolism / Q000473:pathology; D003546:Cysteine Endopeptidases; D010450:Endopeptidases / Q000235:genetics / Q000378:metabolism; D055785:Gene Knockdown Techniques; D006621:Hip Joint / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007719:Knee Joint / Q000378:metabolism / Q000473:pathology; D011475:Prosthesis Failure; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000494:pharmacology; D025842:SUMO-1 Protein / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D013583:Synovial Membrane / Q000378:metabolism* / Q000473:pathology*; D019014:fas Receptor / Q000378:metabolism*
chemical_list: D012333:RNA, Messenger; D034741:RNA, Small Interfering; D025842:SUMO-1 Protein; D019014:fas Receptor; D010450:Endopeptidases; C404512:SENP1 protein, human; D003546:Cysteine Endopeptidases