Artesunate inhibits RANKL-induced osteoclastogenesis and bone resorption in vitro and prevents LPS-induced bone loss in vivo

Cheng Ming Wei, Qian Liu, Fang Ming Song, Xi Xi Lin, Yi Ji Su, Jiake Xu, Lin Huang, Shao Hui Zong, Jin Min Zhao

    Research output: Contribution to journalArticle

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    Abstract

    Osteoclasts are multinuclear giant cells responsible for bone resorption in lytic bone diseases such as osteoporosis, arthritis, periodontitis, and bone tumors. Due to the severe side-effects caused by the currently available drugs, a continuous search for novel bone-protective therapies is essential. Artesunate (Art), the water-soluble derivative of artemisinin has been investigated owing to its anti-malarial properties. However, its effects in osteoclastogenesis have not yet been reported. In this study, Art was shown to inhibit the nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis, the mRNA expression of osteoclastic-specific genes, and resorption pit formation in a dose-dependent manner in primary bone marrow-derived macrophages cells (BMMs). Furthermore, Art markedly blocked the RANKL-induced osteoclastogenesis by attenuating the degradation of IκB and phosphorylation of NF-κB p65. Consistent with the in vitro results, Art inhibited lipopolysaccharide (LPS)-induced bone resorption by suppressing the osteoclastogenesis. Together our data demonstrated that Art inhibits RANKL-induced osteoclastogenesis by suppressing the NF-κB signaling pathway and that it is a promising agent for the treatment of osteolytic diseases.

    LanguageEnglish
    Pages476-485
    Number of pages10
    JournalJournal of Cellular Physiology
    Volume233
    Issue number1
    DOIs
    StatePublished - 1 Jan 2018

    Fingerprint

    Bone Resorption
    Osteogenesis
    Lipopolysaccharides
    Bone
    Bone and Bones
    Periodontitis
    Bone Diseases
    Antimalarials
    Osteoclasts
    Giant Cells
    Phosphorylation
    Macrophages
    Osteoporosis
    Arthritis
    In Vitro Techniques
    artesunate
    Tumors
    Ligands
    Genes
    Messenger RNA

    Cite this

    Wei, Cheng Ming ; Liu, Qian ; Song, Fang Ming ; Lin, Xi Xi ; Su, Yi Ji ; Xu, Jiake ; Huang, Lin ; Zong, Shao Hui ; Zhao, Jin Min. / Artesunate inhibits RANKL-induced osteoclastogenesis and bone resorption in vitro and prevents LPS-induced bone loss in vivo. In: Journal of Cellular Physiology. 2018 ; Vol. 233, No. 1. pp. 476-485
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    abstract = "Osteoclasts are multinuclear giant cells responsible for bone resorption in lytic bone diseases such as osteoporosis, arthritis, periodontitis, and bone tumors. Due to the severe side-effects caused by the currently available drugs, a continuous search for novel bone-protective therapies is essential. Artesunate (Art), the water-soluble derivative of artemisinin has been investigated owing to its anti-malarial properties. However, its effects in osteoclastogenesis have not yet been reported. In this study, Art was shown to inhibit the nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis, the mRNA expression of osteoclastic-specific genes, and resorption pit formation in a dose-dependent manner in primary bone marrow-derived macrophages cells (BMMs). Furthermore, Art markedly blocked the RANKL-induced osteoclastogenesis by attenuating the degradation of IκB and phosphorylation of NF-κB p65. Consistent with the in vitro results, Art inhibited lipopolysaccharide (LPS)-induced bone resorption by suppressing the osteoclastogenesis. Together our data demonstrated that Art inhibits RANKL-induced osteoclastogenesis by suppressing the NF-κB signaling pathway and that it is a promising agent for the treatment of osteolytic diseases.",
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    author = "Wei, {Cheng Ming} and Qian Liu and Song, {Fang Ming} and Lin, {Xi Xi} and Su, {Yi Ji} and Jiake Xu and Lin Huang and Zong, {Shao Hui} and Zhao, {Jin Min}",
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    Wei, CM, Liu, Q, Song, FM, Lin, XX, Su, YJ, Xu, J, Huang, L, Zong, SH & Zhao, JM 2018, 'Artesunate inhibits RANKL-induced osteoclastogenesis and bone resorption in vitro and prevents LPS-induced bone loss in vivo' Journal of Cellular Physiology, vol 233, no. 1, pp. 476-485. DOI: 10.1002/jcp.25907

    Artesunate inhibits RANKL-induced osteoclastogenesis and bone resorption in vitro and prevents LPS-induced bone loss in vivo. / Wei, Cheng Ming; Liu, Qian; Song, Fang Ming; Lin, Xi Xi; Su, Yi Ji; Xu, Jiake; Huang, Lin; Zong, Shao Hui; Zhao, Jin Min.

    In: Journal of Cellular Physiology, Vol. 233, No. 1, 01.01.2018, p. 476-485.

    Research output: Contribution to journalArticle

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    T1 - Artesunate inhibits RANKL-induced osteoclastogenesis and bone resorption in vitro and prevents LPS-induced bone loss in vivo

    AU - Wei,Cheng Ming

    AU - Liu,Qian

    AU - Song,Fang Ming

    AU - Lin,Xi Xi

    AU - Su,Yi Ji

    AU - Xu,Jiake

    AU - Huang,Lin

    AU - Zong,Shao Hui

    AU - Zhao,Jin Min

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    Y1 - 2018/1/1

    N2 - Osteoclasts are multinuclear giant cells responsible for bone resorption in lytic bone diseases such as osteoporosis, arthritis, periodontitis, and bone tumors. Due to the severe side-effects caused by the currently available drugs, a continuous search for novel bone-protective therapies is essential. Artesunate (Art), the water-soluble derivative of artemisinin has been investigated owing to its anti-malarial properties. However, its effects in osteoclastogenesis have not yet been reported. In this study, Art was shown to inhibit the nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis, the mRNA expression of osteoclastic-specific genes, and resorption pit formation in a dose-dependent manner in primary bone marrow-derived macrophages cells (BMMs). Furthermore, Art markedly blocked the RANKL-induced osteoclastogenesis by attenuating the degradation of IκB and phosphorylation of NF-κB p65. Consistent with the in vitro results, Art inhibited lipopolysaccharide (LPS)-induced bone resorption by suppressing the osteoclastogenesis. Together our data demonstrated that Art inhibits RANKL-induced osteoclastogenesis by suppressing the NF-κB signaling pathway and that it is a promising agent for the treatment of osteolytic diseases.

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