The role of endogenous glucocorticoids in bone and cartilage destruction by immunologic processes

内源性糖皮质激素在免疫过程破坏骨和软骨中的作用

• 批准号: 189978752
• 负责人: Professor Dr. Frank Buttgereit
• 金额: --
• 依托单位: Bone Research Program
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2011
• 资助国家: 德国
• 起止时间: 2010-12-31 至 2014-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/189978752?language=en
• 关键词: role; endogenous; glucocorticoids; bone; cartilage

It is unknown whether and how endogenous glucocorticoids contribute to the susceptibilityand severity of rheumatoid arthritis. Using a rodent model of immune-inflammation, we haverecently discovered that the overexpression of 11 ß-hydroxysteroid dehydrogenase type 2(11ß-HSD2), a key regulator of endogenous glucocorticoid action in certain target tissues,attenuates inflammatory activity and joint damage. These results strongly indicate that bothpre-receptor metabolism and the resulting local concentrations of endogenous glucocorticoidsplay an essential role in the regulation and maintenance of inflammation. In the presentproposal we intend to investigate the mechanisms underlying these exciting fmdings in anumber of different models of auto-immune arthritis, using both 11 ß-HSD2 transgenic andosteoblast-specific Gluococorticoid Receptor (GR) knock-out mice in combination with avalidated DNA microarray approach. The overarching aim of this proposal is to establish therole of endogenous glucocorticoids in mediating, regulating and maintaining inflammationand bone/cartilage destmction in autoimmune arthritis.

内源性糖皮质激素是否以及如何促进类风湿关节炎的易感性和严重性尚不清楚。利用啮齿类动物的免疫炎症模型，我们最近发现，11 α-羟基类固醇脱氢酶2型（11 α-HSD 2）的过度表达，在某些靶组织中内源性糖皮质激素作用的关键调节因子，减轻炎症活动和关节损伤。这些结果有力地表明，受体前体代谢和由此产生的内源性糖皮质激素的局部浓度在炎症的调节和维持中起着至关重要的作用。在本研究中，我们打算在多种不同的自身免疫性关节炎模型中研究这些令人兴奋的发现背后的机制，使用11个β-HSD 2转基因和成骨细胞特异性糖皮质激素受体（GR）敲除小鼠结合经验证的DNA微阵列方法。本研究的主要目的是确定内源性糖皮质激素在自身免疫性关节炎中介导、调节和维持炎症和骨/软骨破坏的作用。