期刊
JOURNAL OF PHARMACOLOGICAL SCIENCES
卷 137, 期 1, 页码 76-85出版社
JAPANESE PHARMACOLOGICAL SOC
DOI: 10.1016/j.jphs.2018.03.007
关键词
Postmenopausal osteoporosis (POP); Oleanolic acid (OA); Ovariectomy (OVX); Osteoclastogenesis; Bone resorption
资金
- National Natural Science foundation of China [81673991, 81603643, 81774329, 81503590, 81528022]
- Longhua Innovation Team Program [LYCX-01]
- Longhua Medical Scholar [LYTD-38]
- Xinlin young scholar training program [RC-2017-02-01]
- Innovative Research team of ministry of science and technology of China [IRT1270]
Postmenopausal 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-kappa B, JNK, p38, ERK and Alt 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), tartrate-resistant acid phosphatase (TRAP) and carbonic anhydrase ll (Car2). This work has elucidated the molecular mechanism of OA in RANKL-mediated osteoclastogenesis and revealed the promising potential of OA to be further developed as a new drug to prevent and treat POP. (C) 2018 The Authors. Production and hosting by Elsevier B.V. on behalf of Japanese Pharmacological Society.
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