Oleanolic acid exerts bone protective effects in ovariectomized mice by inhibiting osteoclastogenesis

Publication date: May 2018Source: Journal of Pharmacological Sciences, Volume 137, Issue 1Author(s): Dongfeng Zhao, Xiaofeng Li, Yongjian Zhao, Ping Qiao, Dezhi Tang, Yan Chen, Chunchun Xue, Chenguang Li, Shufen Liu, Jing Wang, Sheng Lu, Qi Shi, Yan Zhang, Yufeng Dong, Yongjun Wang, Bing Shu, Xu FengAbstractPostmenopausal osteoporosis (POP) is quite prevalent and many new drugs are under development to obtain better therapeutic outcomes. Oleanolic acid (OA) has been reported to prevent bone loss in ovariectomized (OVX) rats by stimulating osteoblastogenesis. One previous study has demonstrated that acetate of OA suppressed lipopolysaccharides (LPS)-induced bone loss in mice. However, the role of OA in the receptor activator of nuclear factor kappa-B ligand (RANKL)-mediated osteoclastogenesis is still not elucidated. Here we show that OA dose-dependently inhibits RANKL-mediated osteoclastogenesis and the formation of functional osteoclasts without impairing the viability and osteoclastic potential in bone marrow macrophages (BMMs). Moreover, OA administration attenuates bone loss in OVX mice by inhibiting osteoclast’s densities. Mechanistically, OA does not affect RANKL-induced activation of the NF-кB, JNK, p38, ERK and Akt pathways, but inhibits the expression of the nuclear factor of activated T-cells c1(NFATc1) and c-Fos. Moreover, OA significantly suppresses the expression of RANKL-activated osteoclast genes encoding matrix metalloproteinase 9 (MMP9), Cathepsin K(Ctsk)...
Source: Journal of Pharmacological Sciences - Category: Drugs & Pharmacology Source Type: research