title: Dioscin inhibits osteoclast differentiation and bone resorption though down-regulating the Akt signaling cascades.
abstract: Bone resorption is the unique function of osteoclasts (OCs) and is critical for both bone homeostasis and pathologic bone diseases including osteoporosis, rheumatoid arthritis and tumor bone metastasis. Thus, searching for natural compounds that may suppress osteoclast formation and/or function is promising for the treatment of osteoclast-related diseases. In this study, we for the first time demonstrated that dioscin suppressed RANKL-mediated osteoclast differentiation and bone resorption in vitro in a dose-dependent manner. The suppressive effect of dioscin is supported by the reduced expression of osteoclast-specific markers. Further molecular analysis revealed that dioscin abrogated AKT phosphorylation, which subsequently impaired RANKL-induced nuclear factor-kappaB (NF-κB) signaling pathway and inhibited NFATc1 transcriptional activity. Moreover, in vivo studies further verified the bone protection activity of dioscin in osteolytic animal model. Together our data demonstrate that dioscin suppressed RANKL-induced osteoclast formation and function through Akt signaling cascades. Therefore, dioscin is a potential natural agent for the treatment of osteoclast-related diseases.
authors: Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedics, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors: Xinhua
authors: X
authors: Qu
authors: Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedics, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors: Zanjing
authors: Z
authors: Zhai
authors: Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedics, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors: Xuqiang
authors: X
authors: Liu
authors: Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedics, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors: Haowei
authors: H
authors: Li
authors: Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedics, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Department of Orthopaedics, Hunan Provincial Tumor Hospital and Tumor Hospital of Xiangya School of Medicine, Central South University, Changsha, China.
authors: Zhengxiao
authors: Z
authors: Ouyang
authors: Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedics, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors: Chuanlong
authors: C
authors: Wu
authors: Department of Orthopaedic Surgery, The Central Hospital of Xuzhou, Affiliated Hospital of Medical Collage of Southeast University, Xuzhou, China.
authors: Guangwang
authors: G
authors: Liu
authors: Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedics, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors: Qiming
authors: Q
authors: Fan
authors: Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedics, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors: Tingting
authors: T
authors: Tang
authors: Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedics, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. Electronic address: dr.qinan@gmail.com.
authors: An
authors: A
authors: Qin
authors: Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedics, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. Electronic address: krdai@163.com.
authors: Kerong
authors: K
authors: Dai
mesh_terms: D000818:Animals; D001862:Bone Resorption / Q000378:metabolism* / Q000517:prevention & control; D002454:Cell Differentiation / Q000187:drug effects; D004144:Diosgenin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D015536:Down-Regulation / Q000187:drug effects; D051379:Mice; D010006:Osteoblasts / Q000378:metabolism* / Q000473:pathology*; D010010:Osteoclasts / Q000378:metabolism* / Q000473:pathology*; D010012:Osteogenesis / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D016896:Treatment Outcome
chemical_list: C019357:dioscin; D051057:Proto-Oncogene Proteins c-akt; D004144:Diosgenin
keywords: AKT cascades; Dioscin; Osteoclast; Osteolysis