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Recently, Wu zhaoqiu's team from the school of basic medicine and clinical pharmacy published on nature communications the title of "terminal ZEB1 promotes angiogenes is dependent bone formation and reverses The key role of zinc finger transcription factor ZEB1 in bone angiogenesis osteogenesis and osteoporosis treatment was revealed. Associate Professor Fu Rong, Ph.D. student LV Wencong, master student Xu Ying and Gong Muyun are the co authors of this paper, and Professor Wu zhaoqiu is the corresponding author. Prof. Lu Tao, vice president, Prof. Guo Qinglong, President of the basic hospital, Prof. Mo ran of the Chinese Academy of pharmacy, Prof. Wang Liming, chief physician of orthopaedic department of Nanjing First Hospital, etc. also made important contributions to this paper.
In this study, we first reported that the zinc finger transcription factor ZEB1 was highly expressed in the endothelial cells of H-type bone vessels of normal mice, but low or no expression in L-type bone vessels and other non skeletal soft tissues, and down regulated in the H-type bone vessels of old mice. Using the newly constructed endothelial cell specific ZEB1 knockout mice model, we found that the density of H-type bone vessels decreased, the number of bone progenitor cells decreased, bone formation and bone mass decreased in ZEB1 knockout mice. It was found that the knockout of ZEB1 inhibited the recruitment of histone acetyltransferase CBP / P300 to the promoters of notch and Dll4 genes, down regulated their transcription and translation, inhibited Notch / Dll4 signaling pathway, and then inhibited the angiogenesis of bone and its associated bone formation. Further study found that the expression of ZEB1 in H-type bone endothelial cells of osteoporosis patients and ovariectomized osteoporosis mice was significantly down regulated. The gene delivery system gave ZEB1 gene to ovariectomized mice significantly increased the number of H-type blood vessels, enhanced their bone formation ability, and effectively resisted the bone loss induced by ovariectomy.
This work was supported by the general program and major research program cultivation program of NSFC, the "outstanding youth" program of NSFC, the innovation team and individual program of "mass entrepreneurship and innovation" program of Jiangsu Province, the "double first-class" innovation peak team program of the school, and the independent innovation program of national heavy laboratory.
Contributor: College of basic medicine and clinical pharmacy
Author: he Yuxian
Source: China Pharmaceutical University
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