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Deguelin inhibits RANKL‐induced osteoclastogenesis in vitro and prevents inflammation‐mediated bone loss in vivo
Author(s) -
Zhang Tan,
Zhao Kangxian,
Han Weiqi,
Yang Wanlei,
Lu Xuanyuan,
Liu Qian,
Li Xiucheng,
Qian Yu
Publication year - 2019
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.27087
Subject(s) - rankl , bone resorption , chemistry , microbiology and biotechnology , nf κb , cancer research , in vivo , activator (genetics) , transcription factor , osteoclast , in vitro , receptor , signal transduction , endocrinology , biology , biochemistry , gene
Excessive bone resorption by osteoclasts (OCs) plays an important role in lytic bone diseases, such as osteoporosis. Although the pharmacological treatment of osteoporosis has been extensively developed, alternative treatments are still needed. Deguelin, a rotenoid isolated from several plant species, is a strong antitumor agent; however, its effect on OCs remains unclear. To the best of our knowledge, this is the first study to report that deguelin inhibits the receptor activator of nuclear factor‐κB (NF‐κB) ligand (RANKL)‐induced osteoclastogenesis, messenger RNA expression of osteoclastic‐specific genes, and osteoclastic bone resorption, in primary bone marrow‐derived macrophages. At the molecular level, deguelin markedly blocked RANKL‐induced osteoclastogenesis by attenuating the phosphorylation of NF‐κB p65 and inhibiting p65 nuclear translocation. In addition, deguelin suppressed the downstream expression of nuclear factor of activated T‐cell cytoplasmic 1, which is a crucial transcription factor in OC differentiation. Consistent with the in vitro results, deguelin inhibited lipopolysaccharide‐induced bone resorption by suppressing osteoclastogenesis. Taken together, our findings reveal that deguelin has antiosteoclastic effects in vitro and in vivo and possesses potential as a new therapeutic option for osteolytic bone diseases.