破骨细胞
兰克尔
骨吸收
化学
伞形酮
蛋白激酶B
体内
细胞生物学
骨质疏松症
脂多糖
癌症研究
骨重建
NF-κB
组织蛋白酶K
骨溶解
药理学
信号转导
内分泌学
生物化学
医学
激活剂(遗传学)
生物
体外
受体
牙科
香豆素
有机化学
生物技术
作者
Sung Chul Kwak,Jong Min Baek,Chang Hoon Lee,Kwon‐Ha Yoon,Myeung Su Lee,Ju‐Young Kim
摘要
Excessive bone resorption plays a central role in the development of inflammatory bone diseases, including osteoporosis and rheumatoid arthritis. Thus, identification of agents that can effectively suppress excessive osteoclast formation and function is crucial for the prevention and treatment of inflammatory bone loss. Umbelliferone (Umb), a derivative of coumarin, is a natural bioactive compound with anti-inflammatory and antioxidant properties. However, the effect of Umb on metabolic bone diseases is unknown. In this study, we found that Umb exhibited a strong inhibitory effect on lipopolysaccharide (LPS)-induced inflammatory bone loss in vivo. Histological analysis confirmed that Umb prevented trabecular bone matrix degradation and osteoclast formation in bone tissue. In addition, Umb suppressed RANKL-induced osteoclast differentiation and abrogated bone resorption. We found that the anti-osteoclastic and anti-resorptive activities of Umb are mediated via suppression of the RANKL-induced Akt-c-Fos-NFATc1 signaling pathway and the attenuation of osteoclast-specific genes, such as TRAP, OSCAR, ATP6v0d2, and CtsK. In particular, Umb downregulated the stability of c-Fos and NFATc1 proteins, but did not suppress the expression of their mRNAs. These results indicate that Umb may be a potential therapeutic agent for inflammatory bone diseases associated with abnormal osteoclast formation and function.
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