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Scutellarein inhibits RANKL-induced osteoclast formation in vitro and prevents LPS-induced bone loss in vivo
Authors:Fangsheng Fu  Siyuan Shao  Ziyi Wang  Fangming Song  Xixi Lin  Jiaxin Ding  Chen Li  Zuoxing Wu  Kai Li  Yu Xiao  Yiji Su  Jinmin Zhao  Qian Liu  Jiake Xu
Affiliation:1. School of Biomedical Sciences, The University of Western Australia, Perth, Western Australia, Australia;2. Research Centre for Regenerative Medicine, Guangxi Key Laboratory of Regenerative Medicine, Guangxi Medical University, Nanning, Guangxi, China

School of Biomedical Sciences, The University of Western Australia, Perth, Western Australia, Australia;3. Research Centre for Regenerative Medicine, Guangxi Key Laboratory of Regenerative Medicine, Guangxi Medical University, Nanning, Guangxi, China;4. Department of Rehabilitation Medicine, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China;5. Research Centre for Regenerative Medicine, Guangxi Key Laboratory of Regenerative Medicine, Guangxi Medical University, Nanning, Guangxi, China

Department of Trauma Orthopedic and Hand Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China

Abstract:Osteoporosis, arthritis, Peget's disease, bone tumor, periprosthetic joint infection, and periprosthetic loosening have a common characteristic of osteolysis, which is characterized by the enhanced osteoclastic bone resorptive function. At present, the treatment target of these diseases is to interfere with osteoclastic formation and function. Scutellarein (Scu), a flavonoids compound, can inhibit the progress of tumor and inflammation. However, the role of Scu in inflammatory osteolysis isn’t elucidated clearly. Our study showed that Scu inhibited bone destruction induced by LPS in vivo and OC morphology and function induced by RANKL in vitro. Mechanistic studies revealed that Scu suppressed osteoclastic marker gene expression by RANKL-induced, such as Ctsk9, Mmp9, Acp5, and Atp6v0d2. In addition, we found that the inhibition effects of osteoclastogenesis and bone resorption function of Scu were mediated via attenuating NF-κB and NFAT signaling pathways. In conclusion, the results showed that Scu may become a potential new drug for the treatment of inflammatory osteolysis.
Keywords:NFATc1  NF-κB  osteoclast (OC)  osteolysis  scutellarein (Scu)
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