Gastrodin inhibits osteoclastogenesis via down-regulating the NFATc1 signaling pathway and stimulates osseointegration in vitro.
Bone is a rigid yet dynamic organ, and this dynamism is mediated by the delicate balance between osteoclastic bone resorption and osteoblastic bone formation. However, excessive activation of osteoclasts is responsible for many bone diseases such as osteoporosis, Paget disease, and tumor bone metastasis. Agents that could inhibit osteoclast formation or function are regarded as promising alternatives to treat osteoclast-related diseases. Recently, traditional Chinese medicine has attracted attention because of its multiple activities in bone metabolism. Among them, gastrodin has been reported as an anti-osteoporosis agent that reduces reactive oxygen species. However, the direct action of gastrodin on osteoclast differentiation and bone resorption, and its underlying molecular mechanism, remain unknown. In this study, we investigated the effects of gastrodin on receptor activator NF-κB ligand (RANKL)-activated osteoclasts formation and bone resorption. Our results showed that gastrodin retarded RANKL-induced osteoclast differentiation efficiently by downregulating transcriptional and translational expression of nuclear factor of activated T cells cl (NFATc1), a major factor in RANKL-mediated osteoclastogenesis. Meanwhile, gastrodin prevented osteoclast maturation and migration by inhibiting the gene expression of dendrocyte expressed seven transmembrane protein (DC-STAMP), an osteoclastic-specific gene that controls cells fusion and movement. And gastrodin prevented RANKL-induced osteoclastic bone erosion in vitro. In addition, gastrodin also stimulated bone mesenchymal stem cell (BMSC) spreading and osseointegration in titanium plate. In summary, gastrodin could prevent osteoclasts formation and bone resorption via blockage of NFATc1 activity, and stimulate osseointegration in vitro. Gastrodin could be developed as a potent phytochemical candidate to treat osteolytic diseases.
Department of Orthopaedics, The Second Xiangya Hospital, Central South University, No.139 Middle Renmin Road, Changsha, Hunan 410011, PR China.
Feng
F
Zhou
Department of Orthopaedics, The Second Xiangya Hospital, Central South University, No.139 Middle Renmin Road, Changsha, Hunan 410011, PR China.
Yi
Y
Shen
Department of Orthopaedics, The Second Xiangya Hospital, Central South University, No.139 Middle Renmin Road, Changsha, Hunan 410011, PR China.
Bo
B
Liu
Department of Orthopaedics, The Second Xiangya Hospital, Central South University, No.139 Middle Renmin Road, Changsha, Hunan 410011, PR China.
Xia
X
Chen
Department of Orthopaedics, The Second Xiangya Hospital, Central South University, No.139 Middle Renmin Road, Changsha, Hunan 410011, PR China.
Lu
L
Wan
Department of Orthopaedics, The Second Xiangya Hospital, Central South University, No.139 Middle Renmin Road, Changsha, Hunan 410011, PR China. Electronic address: xyeypd@163.com.
Dan
D
Peng
D000818:Animals; D001592:Benzyl Alcohols / Q000008:administration & dosage*; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D005960:Glucosides / Q000008:administration & dosage*; D051379:Mice; D008810:Mice, Inbred C57BL; D016348:Osseointegration / Q000187:drug effects / Q000502:physiology*; D010010:Osteoclasts / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D010012:Osteogenesis / Q000187:drug effects / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*
D001592:Benzyl Alcohols; D005960:Glucosides; C045345:gastrodin
Differentiation; Gastrodin; NFATc1; Osseointegration; Osteoclasts