骨质疏松症
雌激素
肠道菌群
免疫系统
医学
骨重建
骨免疫学
内科学
内分泌学
生物
免疫学
受体
激活剂(遗传学)
兰克尔
作者
Chuan Chen,Hehua Lei,Yitao Zhao,Yu He,Hou-Feng Zheng,Ce Zhang,Zheng Cao,Fang Wu,Gui Chen,Yuanlin Song,Cui Zhang,Jian Zhou,Yu‐Jing Lu,Denghui Xie,Limin Zhang
标识
DOI:10.1016/j.ejphar.2023.175868
摘要
Postmenopausal osteoporosis stems mainly from estrogen deficiency leading to a gut microbiome-dependent disruption of host systemic immunity. However, the underlying mechanisms of estrogen deficiency-induced bone loss remain elusive and novel pharmaceutical intervention strategies for osteoporosis are needed. Here we reveal that ovariectomy (ovx)-induced estrogen deficiency in C57BL/6 mice causes significant disruption of gut microbiota composition, consequently leading to marked destruction of intestinal barrier function and gut leakage. As a result, signals transportation between intestinal microbiota and T cells from the gut to bone marrow is identified to contribute to osteoclastogenesis in ovx mice. Notably, we show that icariside I (GH01), a novel small molecule naturally occurring in Herbal Epimedium, has potential to alleviate or prevent ovx-induced bone loss in mice through regulation of gut-bone signaling axis. We find that GH01 treatment can effectively restore the gut microbiota composition, intestinal barrier function and host immune status markedly altered in ovx mice, thus significantly ameliorating bone loss and osteoporosis. These findings not only provide systematic understanding of the gut-immunity-bone axis-associated pathophysiology of osteoporosis, but also demonstrate the high potential of GH01 for osteoporosis treatment by targeting the gut-bone signaling axis.
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