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

小泛素样修饰剂 SUMO-1 对类风湿性关节炎炎症性骨破坏的调节

• 批准号: 276356405
• 负责人: Professor Dr. Thomas Pap
• 金额: --
• 依托单位: Institut für Muskuloskelettale Medizin
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2015
• 资助国家: 德国
• 起止时间: 2014-12-31 至 2018-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/276356405?language=en
• 关键词: Regulation; inflammatory; bone; destruction; rheumatoid

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.

炎症是类风湿性关节炎（RA）中进行性骨破坏的主要驱动力，但在这些条件下调节和调节破骨细胞生成的机制仍不完全清楚。我们在以前的工作中已经表明，小泛素样修饰物SUMO-1的表达增加有助于RA的炎症反应，来自教师资助项目的数据表明，SUMO-1敲除小鼠中SUMO-1的丢失与破骨细胞生成减少有关。基于这些结果，我们希望研究SUMO-1在RA炎性骨破坏中的作用。除了体外分析SUMO-1缺陷和突变细胞中的破骨细胞生成外，我们还将使用SUMO-1 k.o.与转基因动物杂交的小鼠，其中TNF α的过度表达导致RA样关节炎。这些数据不仅将为炎症性骨重建提供新的见解，而且可能为这种疾病的新治疗方法铺平道路。

项目成果

02.14 Small ubiquitin related modifier-1 (sumo-1) regulates osteoclast differentiation

02 14â小泛素相关修饰物-1 (sumo-1) 调节破骨细胞分化

• DOI: 10.1136/annrheumdis-2016-211050.14
• 发表时间: 2017
• 期刊: Annals of the Rheumatic Diseases
• 影响因子: 27.4
• 作者: Frank S;de Gorter D;Umlauf D;Jänne O;Dankbar B
• 通讯作者: Dankbar B

The role of stromal cells in inflammatory bone loss

• DOI: 10.1111/cei.12979
• 发表时间: 2017-07
• 期刊: Clinical & Experimental Immunology
• 影响因子: 4.6
• 作者: C. Wehmeyer;T. Pap;C. Buckley;A. Naylor