慢性病和骨关节炎之间的疾病修饰相互作用:一种新的并发症小鼠模型
Sohel M Julovi1,2, Aiken Dao2,3, Katie Trinh4,2
1Kidney Injury Group, Centre for Transplant and Renal Research, Westmead Institute for Medical Research, Westmead, New South Wales, Australia sohel.julovi@sydney.edu.au natasha.rogers@health.nsw.gov.au.
RMD open
|August 10, 2023
概括
这项研究开发了一种共患慢性病 (CKD) 和骨关节炎 (OA) 的临床前模型,揭示了双向疾病相互作用. 调查结果显示,CKD和OA显著地相互影响.
科学领域:
- 脏病学和风湿病学
- 翻译医学是一种翻译医学.
- 临床前疾病建模模型
背景情况:
- 伴随性慢性病 (CKD) 和骨关节炎 (OA) 的全球患病率正在上升.
- 由于共同的风险因素,了解并发CKD-OA的机制和后果至关重要.
- 目前关于CKD和OA之间的双向相互作用的知识是有限的.
研究的目的:
- 开发一种新的临床前模型,用于共发性CKD和OA.
- 在这个模型中研究CKD和OA之间的疾病修饰相互作用.
- 阐明同时出现CKD和OA的病理后果.
主要方法:
- 在雄性C57BL/6小鼠中建立了一个5/6腎切除 (5/6Nx) 模型,以诱导CKD.
- 骨关节炎是通过介质半月体 (DMM) 的不稳定或假手术诱导的.
- 疾病评估包括组织学,微型CT,免疫组织化学和12周血清分析.
主要成果:
- 5/6Nx模型成功地重复了CKD特征,包括纤维化和改变的骨代谢标志物.
- 单独CKD就增加了突MMP-13和下丘脑骨骨质细胞活性,减少了骨体积和密度.
- 同时使用DMM和5/6Nx显示OA病理和骨质细胞激活减少,表明双向疾病修饰.
结论:
- 这项研究提出了第一个共发性CKD-OA的临床前模型.
- 证实了CKD和OA之间显著的双向疾病修饰相互作用.
- 这些发现强调了脏和关节病理之间的复杂相互作用.
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