A natural agent, 5-deoxycajanin, mitigates estrogen-deficiency bone loss via modulating osteoclast-osteoblast homeostasis

• Published in: International immunopharmacology 2024-11, Vol.141, p.112906, Article 112906
• Main Authors: Chen, Zhiwen, Jiang, Mengyu, Mo, Liang, Zhou, Chi, Huang, Haoran, Ma, Chao, Wang, Zhangzheng, Fan, Yinuo, Chen, Zhenqiu, Fang, Bin, Liu, Yuhao
• Format: Article
• Language: English
• Subjects: 5-Deoxycajanin; Bone loss; Osteoblasts; Osteoclasts
• ISSN: 1567-5769; 1878-1705; 1878-1705
• DOI: 10.1016/j.intimp.2024.112906

[Display omitted] •5-Deoxycajanin at the same concentration could inhibit osteoclastogenesis of BMMs and promote osteoblastogenesis of BMSCs via MAPK signaling pathways.•5-Deoxycajanin has potential of alleviating bone loss resulting from hyperactive osteoclasts and hypoactive osteoblasts. Hyperactive osteoclasts and hypoactive osteoblasts usually result in osteolytic conditions such as estrogen-deficiency bone loss. Few natural compounds that both attenuating bone resorption and enhancing bone formation could exert effects on this imbalance. 5-Deoxycajanin (5-D), an isoflavonoid extracted from Cajan leaf with estrogen-like properties, were found to have beneficial pharmacological effects on rebalancing the activities of osteoclasts and osteoblasts. This study revealed that 5-D at the same concentration could inhibit osteoclastogenesis of BMMs and promoted osteoblast differentiation of BMSCs. 5-D not only attenuated the fluorescent formation of RANKL-induced F-actin belts and NFATc1, but also activated ALP and RUNX2 expressions. As to downstream factor expressions, 5-D could block osteoclast-specific genes and proteins including NFATc1 and CTSK, while increased osteogenic genes and proteins including OPG and OCN, as confirmed by Real-time PCR and Western Blotting. Additionally, the network pharmacology and molecular docking identified the involvement of 5-D in the MIF and MAPK signaling pathways and the stable binding between 5-D and MAPK2K1. Further Western blot studies showed that 5-D decreased the phosphorylation of p38 and ERK in osteoclasts, but promoted these phosphorylations in osteoblasts. In a female C57BL/6J mouse model of estrogen deficiency-induced bone loss, 5-D demonstrated efficacy in enhancing BMD through attenuating osteoclast activities and promoting osteogenesis. These results underscore the potential application of 5-D on treating osteolysis resulting from hyperactive osteoclasts and hypoactive osteoblasts, shedding light on modulating osteoclast-osteoblast homeostasis.