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Ellagic acid protects ovariectomy-induced bone loss in mice by inhibiting osteoclast differentiation and bone resorption
Authors:Xixi Lin  Guixin Yuan  Zhaoning Li  Mengyu Zhou  Xianghua Hu  Fangming Song  Siyuan Shao  Fangsheng Fu  Jinmin Zhao  Jiake Xu  Qian Liu  Haotian Feng
Institution:1. Guangxi Key Laboratory of Regenerative Medicine, Guangxi Medical University, Guangxi, China

Department of Trauma Orthopedic and Hand Surgery, Research Centre for Regenerative Medicine, The First Affiliated Hospital of Guangxi Medical University, Guangxi, China;2. Department of Orthopedics, The Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, China;3. Department of orthopedics, Dongguan people's hospital, Dongguan, Guangdong, China;4. Department of Dentistry, The First Affiliated Hospital of Guangxi Medical University, Nanning, China;5. School of Biomedical Sciences, The University of Western Australia, Perth, Western Australia, Australia;6. Department of Trauma Orthopedic and Hand Surgery, Research Centre for Regenerative Medicine, The First Affiliated Hospital of Guangxi Medical University, Guangxi, China;7. Guangxi Key Laboratory of Regenerative Medicine, Guangxi Medical University, Guangxi, China

Abstract:Osteoporosis is a devastating disease that features reduced bone quantity and microstructure, which causes fragility fracture and increases mortality, especially in the aged population. Due to the long-term side-effects of current drugs for osteoporosis, it is of importance to find other safe and effective medications. Ellagic acid (EA) is a phenolic compound found in nut galls, plant extracts, and fruits, and exhibits antioxidant and antineoplastic effects. Here, we showed that EA attenuated the formation and function of osteoclast dose-dependently. The underlying mechanism was further discovered by western blot, immunofluorescence assay, and luciferase assay, which elucidated that EA suppressed osteoclastogenesis and bone resorption mainly through attenuating receptor activator of nuclear factor-κB (NF-κB) ligand-induced NF-κB activation and extracellular signal-regulated kinase signaling pathways, accompanied by decreased protein expression of nuclear factor of activated T-cells calcineurin-dependent 1 and c-Fos. Moreover, EA inhibits osteoclast marker genes expression including Dc-stamp, Ctsk, Atp6v0d2, and Acp5. Intriguingly, we also found that EA treatment could significantly protect ovariectomy-induced bone loss in vivo. Conclusively, this study suggested that EA might have the therapeutic potentiality for preventing or treating osteoporosis.
Keywords:ellagic acid  ERK  NF-κB  osteoclast  osteoporosis  RANKL
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