孟坦丁通过阻断NMDA受体介导的过载和冠状细胞衰老来减轻骨关节炎的发展
Qingmei Cheng1,2,3, Ke He1,2, Junyu Zhu1,2,3
1Hunan Key Laboratory of Joint Degeneration and Injury, Xiangya Hospital, Central South University, Changsha, China.
Journal of orthopaedic translation
|September 16, 2024
概括
美国食品和药物管理局 (FDA) 批准的痴呆症药物孟曼丁有效地阻断N-甲基-D-酸盐 (NMDA) 受体,以减少胆细胞衰老和减缓骨关节炎 (OA) 的进展. 这种重新定位显示了关节炎治疗的前景.
科学领域:
- 生物医学科学 生物医学科学
- 药理学 药理学是指药理学的学科.
- 骨关节炎研究 骨关节炎研究
背景情况:
- 冠状细胞衰老有助于骨关节炎 (OA) 的发展.
- N-甲基-D-酸盐 (NMDA) 受体参与了与OA相关的细胞过程.
- 记忆素和NMDA受体在冠状细胞衰老和OA中的作用尚未得到充分研究.
研究的目的:
- 研究NMDA受体在状细胞衰老和OA中的作用.
- 评估孟坦丁在OA治疗中的治疗潜力.
主要方法:
- 在正常与OA胆红细胞中比较NMDA受体和谷氨酸水平.
- 评估了细胞内,线粒体损伤和冠状细胞衰老.
- 用于NMDA受体功能分析的基因淘汰和激素激活.
- 在体外,体内 (OA小鼠) 和人类队列研究中检查了美曼的疗效.
主要成果:
- 甲状腺冠状细胞显示NMDA受体表达和谷氨酸分泌量增加.
- 激活NMDA受体导致过载,线粒体损伤和冠状细胞衰老.
- 在小鼠中,孟坦丁治疗和NR1敲击降低了的流入,衰老和软骨退化.
- 一项人类队列研究表明,记忆素使用与OA相关的关节置换风险较低有关.
结论:
- 通过NMDA受体的激活,可以通过过载驱动慢性细胞衰老和OA进展.
- 孟坦丁有效抑制NMDA受体活性,减轻冠状细胞衰老和OA.
- 临床和临床前数据支持将孟坦因重新用于骨关节炎治疗.
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