Cordycepin Prevents Bone Loss through Inhibiting Osteoclastogenesis by Scavenging ROS Generation.
Cordycepin was previously reported to have anti-tumor, anti-inflammatory and anti-oxidant activity. However, the potential role of cordycepin in bone metabolism and cell biology of osteoclasts remains unclear. In our study, we focused on the in vitro effects of cordycepin on osteoclastogenesis and its in vivo effects in ovariectomized (OVX) mice. Osteoclast differentiation, formation and fusion were evaluated by Tartrate-resistant acid phosphatase (TRAP) stain, focal adhesion stain and fusion assay, respectively. Osteoclastic bone resorption was evaluated by pit formation assay. Reactive oxygen species (ROS) generation and removal were detected by the ROS assay. OVX mice were orally administered with 10 mg/kg of cordycepin daily for four weeks. In vitro results revealed that cordycepin inhibited receptor activator of nuclear factor κB ligand (RANKL)-induced osteoclast differentiation, formation, fusion and bone resorption activity. We further proved that cordycepin treatments scavenged the generation of ROS, upregulated interferon regulatory factor 8 (IRF-8) and suppressed the activity of nuclear factor of activated T cells c1 (NFATc1) during osteoclastogenesis. In vivo results indicated cordycepin prevents bone loss, rescues bone microarchitecture, and restores bone mineralization in OVX mice. Our observations strongly suggested that cordycepin is an efficient osteoclast inhibitor and hold potential therapeutic value in preventing bone loss among postmenopausal osteoporosis patients.
Department of Orthopedics, Southwest Hospital, Third Military Medical University, Chongqing 400038, China. lance.douce@gmail.com.|Department of Biomedical Materials Science, School of Biomedical Engineering, Third Military Medical University, Gaotanyan Street No. 30, Chongqing 400038, China. lance.douce@gmail.com.
Ce
C
Dou
Department of Biomedical Materials Science, School of Biomedical Engineering, Third Military Medical University, Gaotanyan Street No. 30, Chongqing 400038, China. zhenyacy@163.com.
Zhen
Z
Cao
Department of Biomedical Materials Science, School of Biomedical Engineering, Third Military Medical University, Gaotanyan Street No. 30, Chongqing 400038, China. chrisdawn@163.com.
Ning
N
Ding
Department of Orthopedics, Southwest Hospital, Third Military Medical University, Chongqing 400038, China. tianyonghou@126.com.
Tianyong
T
Hou
Department of Orthopedics, Southwest Hospital, Third Military Medical University, Chongqing 400038, China. luofly1009@21cn.com.
Fei
F
Luo
Department of Biomedical Materials Science, School of Biomedical Engineering, Third Military Medical University, Gaotanyan Street No. 30, Chongqing 400038, China. kangfeilove2007@126.com.
Fei
F
Kang
Department of Biomedical Materials Science, School of Biomedical Engineering, Third Military Medical University, Gaotanyan Street No. 30, Chongqing 400038, China. xcyang@tmmu.edu.cn.
Xiaochao
X
Yang
Department of Biomedical Materials Science, School of Biomedical Engineering, Third Military Medical University, Gaotanyan Street No. 30, Chongqing 400038, China. jh_tmmu@126.com.
Hong
H
Jiang
Department of Orthopedics, Southwest Hospital, Third Military Medical University, Chongqing 400038, China. xiezhao54981@163.com.
Zhao
Z
Xie
Research Center for Molecular Medicine, Kunming University, Kunming 650000, China. humin999@foxmail.com.
Min
M
Hu
Department of Orthopedics, Southwest Hospital, Third Military Medical University, Chongqing 400038, China. xujianzhong1962@163.com.
Jianzhong
J
Xu
Department of Biomedical Materials Science, School of Biomedical Engineering, Third Military Medical University, Gaotanyan Street No. 30, Chongqing 400038, China. dongshiwu@163.com.
Shiwu
S
Dong
D000818:Animals; D015519:Bone Density / Q000187:drug effects*; D002448:Cell Adhesion; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003839:Deoxyadenosines / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D016166:Free Radical Scavengers / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D015394:Molecular Structure; D010010:Osteoclasts / Q000187:drug effects* / Q000502:physiology; D010052:Ovariectomy; D053245:RANK Ligand / Q000235:genetics / Q000378:metabolism; D000067996:RAW 264.7 Cells; D017382:Reactive Oxygen Species / Q000378:metabolism*
D003839:Deoxyadenosines; D016166:Free Radical Scavengers; D053245:RANK Ligand; D017382:Reactive Oxygen Species; C505689:Tnfsf11 protein, mouse; C058120:cordycepin
IRF-8; ROS; cordycepin; osteoclasts; osteoporosis