Inhibition of RANKL-induced osteoclastogenesis through the suppression of the ERK signaling pathway by astragaloside IV and attenuation of titanium-particle-induced osteolysis.
Astragaloside IV (AS-IV) is a natural plant extract that enhances osteoblast activity, and therefore, has the potential to treat osteoclast‑related diseases. Such diseases include osteoporosis, periodontal disease, rheumatoid arthritis and aseptic prosthesis loosening. However, data associating the effects of AS‑IV on osteoclasts are limited. The aim of the present study was to assess the effect of AS‑IV on osteoclasts in vitro and in vivo. The in vitro studies demonstrated that AS‑IV exerts potent inhibitory effects on the ligand of the receptor activator of nuclear factor‑κB‑induced osteoclastogenesis and revealed the mechanism of action of AS‑IV, which inhibited osteoclastogenesis by suppression of the extracellular signal‑regulated kinase signaling pathway. The in vivo studies proved that AS‑IV attenuated titanium particle‑induced osteolysis in a mouse calvarial model. Collectively, the findings of the study suggest that AS‑IV is a potential natural agent for the treatment of osteoclast-related diseases.
Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
Mingjun
M
Li
Department of Orthopedics, Shanghai Key Laboratory of Orthopedic Implant, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, P.R. China.
Wengang
W
Wang
Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
Li
L
Geng
Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
Yanru
Y
Qin
Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
Wenjie
W
Dong
Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
Xudong
X
Zhang
Department of Orthopedics, Shanghai Key Laboratory of Orthopedic Implant, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, P.R. China.
An
A
Qin
Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
Mingzhi
M
Zhang
D000818:Animals; D002460:Cell Line; D004195:Disease Models, Animal; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D008024:Ligands; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D010010:Osteoclasts / Q000187:drug effects* / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects*; D010014:Osteolysis / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D053245:RANK Ligand / Q000378:metabolism*; D053246:Receptor Activator of Nuclear Factor-kappa B / Q000378:metabolism; D012503:Saponins / Q000494:pharmacology*; D014025:Titanium / Q000494:pharmacology*; D014315:Triterpenes / Q000494:pharmacology*
D008024:Ligands; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D012503:Saponins; C505689:Tnfsf11 protein, mouse; D014315:Triterpenes; C052064:astragaloside A; D014025:Titanium; D048049:Extracellular Signal-Regulated MAP Kinases