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Runt 相关转录因子 2 在牙髓间充质干细胞向成骨细胞分化过程中的诱导受组蛋白去甲基化酶 Jumonji AT-富含相互作用域 1B 的调控。

Runt-Related Transcription Factor 2 Induction During Differentiation of Wharton's Jelly Mesenchymal Stem Cells to Osteoblasts Is Regulated by Jumonji AT-Rich Interactive Domain 1B Histone Demethylase.

机构信息

Laboratory of Stem Cells and Development, Faculty of Sciences, Universidad de Chile, Ñuñoa, Santiago, Chile.

FONDAP Center for Genome Regulation., Santiago, Chile.

出版信息

Stem Cells. 2017 Dec;35(12):2430-2441. doi: 10.1002/stem.2704. Epub 2017 Sep 29.

Abstract

Novel bone regeneration approaches aim to obtain immature osteoblasts from somatic stem cells. Umbilical cord Wharton's jelly mesenchymal stem cells (WJ-MSCs) are an ideal source for cell therapy. Hence, the study of mechanisms involved in WJ-MSC osteoblastic differentiation is crucial to exploit their developmental capacity. Here, we have assessed epigenetic control of the Runt-related transcription factor 2 (RUNX2) osteogenic master regulator gene in WJ-MSC. We present evidence indicating that modulation of RUNX2 expression through preventing Jumonji AT-rich interactive domain 1B (JARID1B) histone demethylase activity is relevant to enhance WJ-MSC osteoblastic potential. Hence, JARID1B loss of function in WJ-MSC results in increased RUNX2/p57 expression. Our data highlight JARID1B activity as a novel target to modulate WJ-MSC osteoblastic differentiation with potential applications in bone tissue engineering. Stem Cells 2017;35:2430-2441.

摘要

新型骨再生方法旨在从体干细胞中获得未成熟的成骨细胞。脐带华通氏胶间充质干细胞(WJ-MSCs)是细胞治疗的理想来源。因此,研究 WJ-MSC 成骨分化中涉及的机制对于开发其发育能力至关重要。在这里,我们评估了 runt 相关转录因子 2(RUNX2)成骨主调控基因的表观遗传控制在 WJ-MSC 中的作用。有证据表明,通过阻止 Jumonji AT 丰富的相互作用域 1B(JARID1B)组蛋白去甲基酶活性来调节 RUNX2 表达与增强 WJ-MSC 成骨潜能有关。因此,WJ-MSC 中 JARID1B 的功能丧失导致 RUNX2/p57 表达增加。我们的数据强调了 JARID1B 活性作为调节 WJ-MSC 成骨分化的新靶点,具有在骨组织工程中的潜在应用。干细胞 2017;35:2430-2441。

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