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. 2018 Jan;233(1):476-485.
doi: 10.1002/jcp.25907. Epub 2017 Aug 17.

Artesunate Inhibits RANKL-induced Osteoclastogenesis and Bone Resorption in Vitro and Prevents LPS-induced Bone Loss in Vivo

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Artesunate Inhibits RANKL-induced Osteoclastogenesis and Bone Resorption in Vitro and Prevents LPS-induced Bone Loss in Vivo

Cheng-Ming Wei et al. J Cell Physiol. .

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.

Keywords: Artesunate; lytic bone diseases; osteoclast; osteoclastogenesis.

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