Regulation of inflammatory bone destruction in rheumatoid arthritis by the small ubiquitin-like modifyer SUMO-1

点击翻译按钮获取中文摘要

Inflammation is a major driving force behind progressive bone destruction in rheumatoid arthritis (RA) but the mechanisms that regulate and modulate osteoclastogenesis under these conditions are still incompletely understood. We have shown in previous work that the increased expression of the small ubiquitin-like modifier SUMO-1 contributes to the inflammatory response in RA, and data from a faculty funded project indicate that the loss of SUMO-1 in SUMO-1 knockout mice is associated with decreased osteoclastogenesis. Based on these results, we want to study the role of SUMO-1 in inflammatory bone destruction in RA. In addition to in vitro analyses of osteoclastogenesis in SUMO-1 deficient and mutant cells, we will investigate the role of SUMO-1 in vivo using the SUMO-1 k.o. mice crossed with genetically modified animals, in which overexpression of TNFalpha leads to an RA-like arthritis. These data will not only provide new insights into inflammatory bone remodelling but potentially pave the path to novel therapeutic approaches for this disease.