Lysine-Specific Demethylase 4A Regulates Osteogenic Differentiation via Regulating the Binding Ability of H3K9me3 with the Promoters of Runx2, Osterix and Osteocalcin
Lysine-Specific Demethylase 4A Regulates Osteogenic Differentiation via Regulating the Binding Ability of H3K9me3 with the Promoters of Runx2, Osterix and Osteocalcin
复制标题
赖氨酸特异性去甲基酶 4A 通过调节 H3K9me3 与 Runx2、Osterix 和骨钙素启动子的结合能力来调节成骨分化
DOI：
10.1166/jbn.2020.2929
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发表时间：
2020-06-01
影响因子：
2.9
通讯作者：
Huo, Shaochuan
中科院分区：
文献类型：
--
作者：
Qin, Guozhong;Li, Yikai;Huo, Shaochuan
作为表观遗传学的一个研究对象，位于赖氨酸和精氨酸的组蛋白甲基化通过甲基转移酶和去甲基酶进行监督。赖氨酸特异性脱甲基酶4A（KDM4A）包括赖氨酸脱甲基酶，并且对H3K9me3和H3K36me3具有特异性，其能够用于激活组蛋白转录。我们的团队检查了KDM 4A在Sprague道利（SD）大鼠中的表达，并进一步研究了这种现象在本研究中调节成骨变异的机制。KDM4A的过表达促进了骨髓间充质干细胞（BMSC）向成骨细胞分化的过程，而通过抑制Runx2、Osterix、碱性磷酸酶（ALP）和骨钙素（OCN）的表达，抑制了通过成骨细胞敲低分化的过程。敲低KDM4A降低Runx2、osterix和OCN的启动子表达水平，并提高H3K27me3的表达水平。结果表明，KDM4A在成骨细胞的分化中具有关键作用，并且还通过H3K9me3调节Runx2、Osterix和OCN的表达。本研究可能为骨愈合的治疗提供新的见解。
A well-studied subject of epigenetics, the histone methylation located at lysine and arginine is overseen via methyltransferases and demethylases. Lysine-specific demethylase 4A (KDM4A) comprises a lysine demethylase and possesses specificity for H3K9me3 and H3K36me3, which is capable of being used in order to activate histone transcription. Our team examined the expression of KDM4A within Sprague Dawley (SD) rats and further investigated the mechanism via which this phenomena regulates osteogenic variation within the present study. The overexpression of KDM4A facilitated the process of osteoblast differentiation in bone mesenchymal stem cells (BMSC), while the knocking down differentiation via osteoblast was restrained via the suppression of the expression of Runx2, Osterix, alkaline phosphatase (ALP), and osteocalcin (OCN). Knocking down KDM4A lowered levels of the promoter expression of Runx2, osterix, and OCN, and raised levels of H3K27me3 expression. The results demonstrated that KDM4A possesses a crucial role within the differentiation of osteoblasts and furthermore regulates the expression of Runx2, Osterix, and OCN via H3K9me3. The present research may provide new insights into the treatment of bone healing.