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衰老驱动的炎症和热带微环境在骨关节炎患者中印记了大介质干细胞/干细胞

Giuseppe Fusi¹, Michael Constantinides¹, Christina Fissoun¹

¹IRMB, University Montpellier, INSERM, 34295 Montpellier, France.

|July 29, 2023

概括

细胞衰老驱动骨关节炎 (OA) 通过改变介酶体 stromal/干细胞 (MSC). 这项研究揭示了老化的细胞因素如何影响MSC,为OA提供了新的治疗点.

科学领域:

生物医学科学生物医学科学
细胞生物学细胞生物学
类风湿病学类风湿病学

背景情况:

细胞衰老,以炎症和热层变化为特征,驱动诸如骨关节炎 (OA) 等与年龄相关的疾病.
衰老标志物存在于关节细胞中,包括软骨细胞,突触细胞和骨细胞,这表明它在OA病变发生过程中发挥了作用.
骨关节介质干细胞 (MSCs) 对关节健康和修复至关重要,但它们在OA微环境中的命运尚不清楚.

研究的目的:

研究老化驱动的微环境如何影响骨关节介质干细胞/干细胞 (MSCs) 的行为.
通过影响MSCs来确定衰老因素对OA进展有所贡献的分子机制.
探索针对OA中MSC的潜在治疗策略.

主要方法:

来自健康捐赠者的MSCs的基因表达的比较分析.
在体外慢性暴露MSCs的干扰素 (IFN-γ) 和转化生长因子β1 (TGFβ1),从衰老细胞的关键因素.
从OA患者中分离的MSC中分析基因表达特征.

主要成果:

两种IFN-γ和TGFβ1治疗都通过上调细胞循环依赖的激酶抑制剂来降低MSC自我更新.
在接受治疗的MSC和OA患者的MSC中发现了一组共享的差异表达基因.
与衰老相关的微环境印记了OA MSCs,改变了它们的母体体基因表达.

结论:

衰老的微环境显著影响骨关节MSC,有助于OA的发病.
印制的OA MSCs表现出改变的母体体基因表达,突出了OA病因学的新方面.
这些发现表明,通过准MSC和老化的微环境,为OA提供新的治疗途径.

关键词:

在MSC中,MSC是MSC.骨关节炎是一种关节炎.衰老是一种老化.

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