在软骨组织工程中,JMJD3和UTX是转基因介质干细胞治疗的关键标
Lyess Allas1, Juliette Aury-Landas1, Quitterie Rochoux-Briet2
1Normandie Univ, UNICAEN, UR7451 BioConnecT, 14000 Caen, France.
概括
基因组脱甲基酶JMJD3和UTX是软骨发育的关键. JMJD3对于体生成至关重要,而这两种疗法都能增强基因改性介质干细胞疗法,用于软骨组织工程.
科学领域:
- 表观遗传学和再生医学
- 分子生物学和细胞分化
背景情况:
- 基斯甲基化对软骨发育和工程至关重要.
- 基因组H3氨酸27三甲基化 (H3K27me3) 是一个由脱甲基酶调节的关键表观遗传标记.
- 介质细胞干细胞 (MSC) 疗法对软骨组织工程具有前景.
研究的目的:
- 调查JMJD3 (KDM6B) 和UTX (KDM6A) 在体生成中的作用.
- 评估这些H3K27me3脱甲基酶在基因修饰的MSC疗法中用于软骨再生的应用.
主要方法:
- 研究了在人类骨髓衍生的MSC (hBM-MSCs) 中的chondrogenesis期间的JMJD3和UTX表达和功能.
- 评估了JMJD3和UTX对原体基因表达和分化的影响.
- 研究了JMJD3和UTX的短暂转导在基因修饰的MSC治疗中对软骨形成的影响.
主要成果:
- JMJD3是上调调节的,对于hBM-MSC的冠状体发生是必不可少的;UTX是不可缺少的.
- 无论是JMJD3还是UTX都会去甲基化相似的基因位点,促进原体基因表达,表明功能冗余.
- 在基因改性MSC疗法中,JMJD3和UTX在基因发生过程中的过度表达增强了软骨盘的形成和II型原蛋白含量.
结论:
- JMJD3在基生成中发挥着关键作用,而UTX在关键性方面不那么重要,但功能上是多余的.
- JMJD3和UTX是提高软骨组织工程的基因改造MSC疗法的有希望的目标.
- 暂时的JMJD3转导是一种改善软骨再生结果的潜在策略.
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