Xu Cuidi, Shi Hongli, Jiang Xin, Fan Yongqian, Huang Donghui, Qi Xinming, Cheng Qun
Department of Osteoporosis and Bone Disease, Huadong Hospital Affiliated to Fudan University, Research Section of Geriatric Metabolic Bone Disease, Shanghai Geriatric Institute, Shanghai, China.
Department of Orthopedics, Huadong Hospital Affiliated to Fudan University, Shanghai, China.
Front Mol Biosci. 2021 May 24;8:682728. doi: 10.3389/fmolb.2021.682728. eCollection 2021.
Zinc finger E-box-binding homebox 1 (ZEB1) is a zinc-finger transcription factor best known for its role in promoting the epithelial-mesenchymal transition, which is also related to osteogenesis. Here, ZEB1 was investigated for its role in the commitment of bone marrow mesenchymal stem cells (BMSCs) to osteoblasts. , ZEB1 expression decreased following osteogenic differentiation. Furthermore, silencing of ZEB1 in BMSCs promoted osteogenic activity and mineralization. The increase in osteogenic differentiation induced by si-ZEB1 could be partly rescued by the inhibition of Wnt/β-catenin (si-β-catenin). , knockdown of ZEB1 in BMSCs inhibited the rapid bone loss of ovariectomized (OVX) mice. ZEB1 expression has also been negatively associated with bone mass and bone formation in postmenopausal women. In conclusion, ZEB1 is an essential transcription factor in BMSC differentiation and may serve as a potential anabolic strategy for treating and preventing postmenopausal osteoporosis (PMOP).
锌指E盒结合同源盒蛋白1(ZEB1)是一种锌指转录因子,因其在促进上皮-间质转化中的作用而最为人所知,上皮-间质转化也与骨生成有关。在此,研究了ZEB1在骨髓间充质干细胞(BMSC)向成骨细胞分化过程中的作用。成骨分化后,ZEB1表达降低。此外,沉默BMSC中的ZEB1可促进成骨活性和矿化。si-ZEB1诱导的成骨分化增加可通过抑制Wnt/β-连环蛋白(si-β-连环蛋白)部分挽救。此外,敲低BMSC中的ZEB1可抑制去卵巢(OVX)小鼠的快速骨质流失。绝经后女性的ZEB1表达也与骨量和骨形成呈负相关。总之,ZEB1是BMSC分化中的一种重要转录因子,可能作为治疗和预防绝经后骨质疏松症(PMOP)的潜在合成代谢策略。