破骨细胞
兰克尔
骨吸收
骨质疏松症
体内
化学
去卵巢大鼠
成骨细胞
p38丝裂原活化蛋白激酶
癌症研究
内分泌学
药理学
细胞生物学
内科学
MAPK/ERK通路
信号转导
体外
医学
受体
生物
生物化学
雌激素
激活剂(遗传学)
生物技术
作者
Binhua Zou,Jianjian Zheng,Wende Deng,Yanhui Tan,Ligang Jie,Qing Yuan,Qin Yang,Minhong Ke,Zongbao Ding,Yan Chen,Yu Q,Xiaojuan Li
出处
期刊:Phytomedicine
[Elsevier]
日期:2021-01-01
卷期号:80: 153377-153377
被引量:20
标识
DOI:10.1016/j.phymed.2020.153377
摘要
Osteoporosis is a threat to aged people who have excessive osteoclast activation and bone resorption, subsequently causing fracture and even disability. Inhibiting osteoclast differentiation and absorptive functions has become an efficient approach to treat osteoporosis, but osteoclast-targeting inhibitors available clinically remain rare. Kirenol (Kir), a bioactive diterpenoid derived from an antirheumatic Chinese herbal medicine Herba Siegesbeckiae, can treat collagen-induced arthritis in vivo and promote osteoblast differentiation in vitro, while the effects of Kir on osteoclasts are still unclear. We explore the role of Kir on RANKL-induced osteoclastogenesis in vitro and bone loss in vivo. The in vitro effects of Kir on osteoclast differentiation, bone resorption and the underlying mechanisms were evaluated with bone marrow-derived macrophages (BMMs). In vivo experiments were performed using an ovariectomy (OVX)-induced osteoporosis model. We found that Kir remarkably inhibited osteoclast generation and bone resorption in vitro. Mechanistically, Kir significantly inhibited F-actinring formation and repressed RANKL-induced NF-κB p65 activation and p-p38, p-ERK and c-Fos expression. Moreover, Kir inhibited both the expression and nuclear translocation of NFATc1. Ca2+ oscillation and caveolin-1 (Cav-1) were also reduced by Kir during osteoclastogenesis in vitro. Consistent with these findings, 2–10 mg/kg Kir attenuated OVX-induced osteoporosis in vivo as evidenced by decreased osteoclast numbers and downregulated Cav-1 and NFATc1 expression. Kir suppresses osteoclastogenesis and the Cav-1/NFATc1 signaling pathway both in vitro and in vivo and protects against OVX-induced osteoporosis. Our findings reveal Kir as a potential safe oral treatment for osteoporosis.
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