H19 和 Foxc2 通过 Wnt-β-catenin 通路协同促进骨髓间充质干细胞的成骨分化。
H19 and Foxc2 synergistically promotes osteogenic differentiation of BMSCs via Wnt-β-catenin pathway.
机构信息
Department of Geriatrics, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China.
The Institute of Hard Tissue Development and Regeneration, Harbin Medical University, Harbin, Heilongjiang, China.
出版信息
J Cell Physiol. 2019 Aug;234(8):13799-13806. doi: 10.1002/jcp.28060. Epub 2019 Jan 11.
OBJECTIVE
To investigate the mechanism of H19 on the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs).
METHODS
Ovariectomized (OVX) mouse model was established. RNA immunoprecipitation and RNA pull-down assays were performed to determine the correlation between H19 and forkhead box C2 (Foxc2). Chromatin immunoprecipitation assay was used to identify whether Foxc2 binds to the Wnt4 promoter region. Molecules expressions were measured by quantitative real-time polymerase chain reaction and western blot.
RESULTS
We found that H19 expression was reduced in the serum of patients with postmenopausal osteoporosis and BMSCs of OVX mice, and overexpression of H19 promoted osteogenic differentiation of BMSCs. Additionally, Foxc2 could bind to the Wnt4 promoter and promote its transcription. We also showed that H19 could bind to Foxc2, and H19/Foxc2 regulated Wnt promoter expression in a synergistic fashion, and H19/Foxc2 regulated osteogenic differentiation of BMSCs through Wnt-β-catenin pathway.
CONCLUSION
H19 and Foxc2 synergistically promoted osteogenic differentiation of BMSCs via Wnt-β-catenin pathway.
目的
研究 H19 对骨髓间充质干细胞（BMSCs）成骨分化的作用机制。
方法
建立去卵巢（OVX）小鼠模型。采用 RNA 免疫沉淀和 RNA 下拉实验来确定 H19 与叉头框蛋白 C2（Foxc2）之间的相关性。染色质免疫沉淀实验用于鉴定 Foxc2 是否结合 Wnt4 启动子区域。通过实时定量聚合酶链反应和 Western blot 检测分子表达。
结果
我们发现绝经后骨质疏松症患者的血清和 OVX 小鼠的 BMSCs 中 H19 的表达降低，而过表达 H19 则促进 BMSCs 的成骨分化。此外，Foxc2 可以与 Wnt4 启动子结合并促进其转录。我们还表明，H19 可以与 Foxc2 结合，并且 H19/Foxc2 以协同方式调节 Wnt 启动子的表达，并且 H19/Foxc2 通过 Wnt-β-连环蛋白途径调节 BMSCs 的成骨分化。
结论
H19 和 Foxc2 通过 Wnt-β-连环蛋白途径协同促进 BMSCs 的成骨分化。
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