Fumitremorgin C Attenuates Osteoclast Formation and Function via Suppressing RANKL-Induced Signaling Pathways

Frontiers in Pharmacology

Kai Chen¹  Youqiang Sun²  Jennifer Tickner³  Heng Qiu³  Chao Wang³  Dezhi Song³  Jianmin Guo³  Jiake Xu³  Zhen Cao³  Jun Zou⁴  Yu Yuan⁵  Xi Chen⁶ 

[1]Department of Orthopaedic Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China

[2]Department of Orthopedics, First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, China

[3]School of Biomedical Sciences, University of Western Australia, Perth, WA, Australia

[4]School of Kinesiology, Shanghai University of Sport, Shanghai, China

[5]School of Physical Education and Sports Science, South China Normal University, Guangzhou, China

[6]School of Sports Science, Wenzhou Medical University, Wenzhou, China

关键词: fumitremorgin C;    osteoclast;    osteoporosis;    NFATc1;    MAPK;   

DOI  :  10.3389/fphar.2020.00238

来源: DOAJ

【 摘 要 】

Excessive bone resorption conducted by osteoclasts is considered as the main cause of osteoclast-related bone diseases such as osteoporosis. Therefore, the suppression of excessive osteoclast formation and function is one of the strategies to treat osteoclast-related bone diseases. Fumitremorgin C (Fum) is a mycotoxin extracted from Aspergillus fumigatus. It has been shown to have extensive pharmacological properties, but its role in the treatment of osteoclast-related bone diseases remains unclear. In this study, we aim to find out whether Fum can inhibit the receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast formation and function. The results showed that Fum could significantly attenuate osteoclast formation and function at concentrations from 2.5 to 10 µM. The protein expression of bone resorption factors such as NFATc1, cathepsin K, V-ATPase-d2, and c-Fos was suppressed with the treatment of Fum at a concentration of 10 µM. In addition, Fum was also shown to suppress the activity of NF-κB, intracellular reactive oxygen species level, and MAPK pathway. Taken together, the present study showed that Fum could attenuate the formation and function of osteoclast via suppressing RANKL-induced signaling pathways, suggesting that Fum might be a potential novel drug in the treatment of osteoclast-related bone diseases.

【 授权许可】

Unknown