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Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-23664

Meinecke, I; Pap, G; Mendoza, H; Drange, S; Ender, S; Strietholt, S; Gay, R E; Seyfert, C; Ink, B; Gay, S; Pap, T; Peters, M A (2009). Small ubiquitin-like modifier 1 [corrected] mediates the resistance of prosthesis-loosening fibroblast-like synoviocytes against Fas-induced apoptosis. Arthritis and Rheumatism, 60(7):2065-2070.

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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. CONCLUSION: 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.

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Center for Integrative Human Physiology
04 Faculty of Medicine > University Hospital Zurich > Rheumatology Clinic and Institute of Physical Medicine
DDC:570 Life sciences; biology
610 Medicine & health
Language:English
Date:June 2009
Deposited On:04 Nov 2009 14:08
Last Modified:27 Nov 2013 19:19
Publisher:Wiley-Blackwell
ISSN:0004-3591
Additional Information:The definitive version is available at www.blackwell-synergy.com
Publisher DOI:10.1002/art.24633
PubMed ID:19565496
Citations:Web of Science®. Times Cited: 8
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