南京中医药大学常熟附属医院;
间充质细胞又称为间充质干细胞（Mesenchymal stem cells,MSC）、间质干细胞、间叶干细胞，泛指一类具有一定分化潜能、可以分化成多种细胞类型、具有组织修复功能的多能基质细胞群。骨髓间充质细胞分化为成骨细胞是骨形成的关键步骤。然而成骨分化早期阶段所涉及的机制尚不清楚。前期研究发现FHL2是LIM蛋白超家族中LIM-only亚类的成员，在小鼠和人类MSCs中地塞米松诱导的早期成骨细胞分化过程中该亚类显著上调。此外，FHL2可促进成骨细胞转录因子Runx2、碱性磷酸酶（Alkaline phosphatase,ALP）、I型胶原蛋白A1 (Collagen type I alpha 1 chain,COL1A1)的表达以及间充质细胞的细胞外基质矿化（Extracellular matrix mineralization）。本研究使用sh-RNA敲除FHL2观察MSCs中重组腺相关病毒（Recombination adeno-associated virus, rAAV）诱导的成骨细胞标志基因表达情况。结果发现FHL2与β-catenin相互作用，后者是Wnt信号诱导的骨形成中的关键参与者。FHL2-β-catenin相互作用增强了β-catenin核转位和TCF/LEF转录，导致Runx2和ALP表达增加，而Wnt抑制剂DKK1可抑制这种表达。这些结果表明，FHL2是间充质细胞分化成成骨细胞的内源性激活剂，它通过激活Wnt/β-catenin信号依赖性Runx2的表达，介导重组腺相关病毒诱导的间充质干细胞成骨分化。
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基本信息:
DOI：10.13242/j.cnki.bingduxuebao.240269
中图分类号:R580
引用信息:
[1]蒋晓伟,王强,缪逸鸣等.重组腺相关病毒调控间充质干细胞成骨分化的作用机制[J].病毒学报,2025,41(02):479-487.DOI:10.13242/j.cnki.bingduxuebao.240269.
基金信息: