Xia Wenqian, Han Xiao, Wang Lin
Key Laboratory of Human Functional Genomics of Jiangsu Province, Nanjing Medical University, Nanjing, Jiangsu 211166, China.
Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, Jiangsu 210009, China.
J Biomed Res. 2021 Dec 30;36(1):39-47. doi: 10.7555/JBR.35.20210123.
Chronic high glucose (HG) plays a crucial role in the pathogenesis of diabetes-induced osteoporosis by inhibiting the differentiation and proliferation of osteoblasts. This study aims to examine the role of E26 transformation-specific 1 (ETS1) in the inhibition of osteoblast differentiation and proliferation caused by chronic HG, as well as the underlying mechanism. Chronic HG treatment downregulated ETS1 expression and inhibited differentiation and proliferation of MC3T3-E1 cells. Downregulation of ETS1 expression inhibited the differentiation and proliferation of MC3T3-E1 cells under normal glucose conditions, and ETS1 overexpression attenuated the damage to cells exposed to chronic HG. In addition, ETS1 overexpression reversed the decrease in runt-related transcription factor 2 (Runx2) expression in MC3T3-E1 cells treated with chronic HG. Using chromatin immunoprecipitation (ChIP) and luciferase reporter assays, we confirmed that ETS1 directly bound to and increased the activity of the promoter. In summary, our study suggested that ETS1 was involved in the inhibitory effect of chronic HG on osteogenic differentiation and proliferation and may be a potential therapeutic target for diabetes-induced osteoporosis.
慢性高血糖（HG）通过抑制成骨细胞的分化和增殖，在糖尿病性骨质疏松症的发病机制中起关键作用。本研究旨在探讨E26转化特异性1（ETS1）在慢性HG所致成骨细胞分化和增殖抑制中的作用及其潜在机制。慢性HG处理下调了ETS1表达，并抑制了MC3T3-E1细胞的分化和增殖。ETS1表达下调在正常葡萄糖条件下抑制了MC3T3-E1细胞的分化和增殖，而ETS1过表达减轻了慢性HG对细胞的损伤。此外，ETS1过表达逆转了慢性HG处理的MC3T3-E1细胞中与矮小相关转录因子2（Runx2）表达的降低。通过染色质免疫沉淀（ChIP）和荧光素酶报告基因分析，我们证实ETS1直接结合并增强了启动子的活性。总之，我们的研究表明，ETS1参与了慢性HG对成骨分化和增殖的抑制作用，可能是糖尿病性骨质疏松症的一个潜在治疗靶点。
