骨质疏松症
Wnt信号通路
马拉特1
肿瘤坏死因子α
医学
干细胞
癌症研究
内科学
内分泌学
下调和上调
化学
生物
信号转导
细胞生物学
长非编码RNA
生物化学
基因
作者
Feng Lu,Zhengmeng Yang,Nan Hou,Ming Wang,Xuan Lu,Yucong Li,Hai Wang,Yaofeng Wang,Shanshan Bai,Xiaoting Zhang,Yuejun Lin,Yan Xu,Sien Lin,Micky D. Tortorella,Gang Li
摘要
Osteoporosis, a common systematic bone homeostasis disorder related disease, still urgently needs innovative treatment methods. Several natural small molecules were found to be effective therapeutics in osteoporosis. In the present study, quercetin was screened out from a library of natural small molecular compounds by a dual luciferase reporter system. Quercetin was found to upregulate Wnt/β-catenin while inhibiting NF-κB signaling activities, and thereby rescuing osteoporosis-induced tumor necrosis factor alpha (TNFα) impaired BMSCs osteogenesis. Furthermore, a putative functional lncRNA, Malat1, was shown to be a key mediator in quercetin regulated signaling activities and TNFα-impaired BMSCs osteogenesis, as mentioned above. In an ovariectomy (OVX)-induced osteoporosis mouse model, quercetin administration could significantly rescue OVX-induced bone loss and structure deterioration. Serum levels of Malat1 were also obviously rescued in the OVX model after quercetin treatment. In conclusion, our study demonstrated that quercetin could rescue TNFα-impaired BMSCs osteogenesis in vitro and osteoporosis-induced bone loss in vivo, in a Malat1-dependent manner, suggesting that quercetin may serve as a therapeutic candidate for osteoporosis treatment.
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