USP1 inhibitor ML323 enhances osteogenic potential of human dental pulp stem cells
USP1 inhibitor ML323 enhances osteogenic potential of human dental pulp stem cells
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DOI：
10.1016/j.bbrc.2020.05.095
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发表时间：
2020-09-17
影响因子：
3.1
通讯作者：
Choung, Pill-Hoon
中科院分区：
文献类型：
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作者：
Kim, Ji-Youn;Choung, Pill-Hoon
LIM同源框8（LHX 8）在颅面组织（包括骨和牙齿）的胚胎发育期间表达。在先前的研究中，LHX 8的过表达抑制了人牙髓干细胞（DPSC）的骨分化。在这项研究中，进行了cDNA微阵列分析，以揭示在DPSC中响应LHX 8过表达而发生的分子变化，并发现骨诱导剂的可能靶点。有345个差异表达基因（DEG）响应于骨诱导信号和53个DEG响应于LHX 8过表达和骨诱导信号，分别。两种条件下共有38个基因，其中选择了在LHX 8 DPSC中上调但在骨分化DPSC中下调的基因。其中5个有市售抑制剂。在测试的抑制剂中，靶向DNA结合蛋白抑制剂ID-1的ML 323促进DPSC的骨分化。总之，抑制ID-1导致人DPSC的骨生成增加。(C)2020爱思唯尔公司All rights reserved.
LIM homeobox 8 (LHX8) is expressed during embryonic development of craniofacial tissues, including bone and teeth. In a previous study, the overexpression of LHX8 inhibited osteodifferentiation of human dental pulp stem cells (DPSCs). In this study, a cDNA microarray analysis was performed to reveal the molecular changes which occur in response to LHX8 overexpression in DPSCs and discover possible targets for an osteoinductive agent. There were 345 differentially expressed genes (DEGs) in response to osteoinductive signaling and 53 DEGs in response to LHX8 overexpression and osteoinductive signaling, respectively. Thirty-eight genes were common in both conditions, and among these, genes upregulated in LHX8 DPSCs but downregulated in osteodifferentiated DPSCs were chosen. Five of them had commercial inhibitors available. Among the tested inhibitors, ML323, which target DNA-binding protein inhibitor ID-1, promoted osteodifferentiation of DPSCs. In conclusion, inhibition of ID-1 led to increased osteogenesis of human DPSCs. (C) 2020 Elsevier Inc. All rights reserved.