在类风湿性关节炎和骨关节炎中,肌肉和免疫细胞的代谢重编程:治疗可能性
Órlaith C Henry1, Luke A J O'Neill1
1Biomedical Sciences Institute, Trinity College Dublin, Dublin, Ireland.
European journal of immunology
|April 2, 2025
概括
关节细胞的代谢变化导致类风湿性关节炎 (RA) 和骨关节炎 (OA). 针对这些代谢途径为结合组织疾病提供了一个有前途的治疗策略.
科学领域:
- 生物化学 生物化学
- 免疫学 免疫学 免疫学
- 细胞生物学 细胞生物学
背景情况:
- 类风湿性关节炎 (RA) 和骨关节炎 (OA) 涉及纤维细胞样同胞细胞 (FLS),软质细胞和骨质细胞 (OCs) 等 stromal 细胞的代谢重编程.
- 在RA中,FLS显示mTOR激活,葡萄糖分解增加,氧化酸化减少,有助于炎症,血管生成和软骨分解.
- 在OA中,软体细胞表现出与mTOR和NF-κB激活的代谢重新连接,线粒体功能障碍和高血糖分解,促进矩阵降解和血管生成.
研究的目的:
- 为了研究在RA和OA病变发生过程中,肌层细胞中代谢重编程的作用.
- 探索巨细胞衍生的免疫代谢物苏酸和伊塔康酸对树皮细胞功能的影响.
- 突出针对结合组织疾病中的代谢途径的治疗潜力.
主要方法:
- 在RA和OA模型中分析纤维细胞样同胞细胞 (FLS),软质细胞和骨质细胞 (OCs) 的代谢概况.
- 调查免疫代谢物如苏酸和伊塔康酸的信号作用.
- 审查新出现的关于代谢向策略的证据.
主要成果:
- 在RA中FLS表现出mTOR激活,有利于糖解而不是氧化酸化,这促进了炎症和软骨退化.
- 甲状腺冠状细胞表现出代谢转变,包括mTOR/NF-κB激活和增加糖解,导致细胞外基质 (ECM) 降解.
- 免疫代谢物苏酸 (促炎) 和伊塔科纳酸 (抗炎) 调节树皮细胞活性;伊塔科纳酸缺乏与RA严重程度相关.
结论:
- 结构细胞的代谢重编程是RA和OA病变发生的关键驱动因素.
- 免疫代谢物在调节关节内的炎症和代谢过程中起着重要的作用.
- 准细胞代谢是一个有前途的治疗途径,用于治疗关节组织疾病,如RA和OA.
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