Laboratory of Stem Cells and Development, Faculty of Sciences, Universidad de Chile, Ñuñoa, Santiago, Chile.
FONDAP Center for Genome Regulation., Santiago, Chile.
Stem Cells. 2017 Dec;35(12):2430-2441. doi: 10.1002/stem.2704. Epub 2017 Sep 29.
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.
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。