a matrine derivative m54 suppresses osteoclastogenesis and prevents ovariectomy-induced bone loss by targeting ribosomal protein s5

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ID: 166742
2018
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Abstract
Post-menopausal osteoporosis (PMOP) is a metabolic bone disorder characterized by low bone mass and micro-architectural deterioration of bone tissue. The over-activated osteoclastogenesis, which plays an important role in osteoporosis, has become an important therapeutic target. M54 was a bioactive derivative of the Chinese traditional herb matrine. We found that M54 could suppress RANKL-induced osteoclastogenesis in bone marrow mononuclear cells and RAW264.7 cells through suppressing NF-κB, PI3K/AKT, and MAPKs pathways activity in vitro, and prevent ovariectomy-induced bone loss in vivo. Our previous study has proved that ribosomal protein S5 (RPS5) was a direct target of M19, based on which M54 was synthesized. Thus we deduced that M54 also targeted RPS5. During osteoclastogenesis, the RPS5 level in RAW264.7 cells was significantly down-regulated while M54 could maintain its level. After RPS5 was silenced, the inhibitory effects of M54 on osteoclastogenesis were partially compromised, indicating that M54 took effects through targeting RPS5. In summary, M54 was a potential clinical medicine for post-menopause osteoporosis treatment, and RPS5 is a possible key protein in PMOP.
Reference Key
xin2018frontiersa Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors ;Zhi Xin;Cui Jin;Liu Chao;Zhang Zheng;Cao Liehu;Cao Liehu;Pan Panpan;Pan Panpan;Weng Weizong;Weng Weizong;Zhai Xiao;Zhao Qingjie;Hu Honggang;Qin Longjuan;Chen Xiao;Chen Xiao;Su Jiacan;Su Jiacan
Journal chemical research in chinese universities
Year 2018
DOI
10.3389/fphar.2018.00022
URL
http://journal.frontiersin.org/article/10.3389/fphar.2018.00022/full
Keywords
rankl osteoclasts pharmacology

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