Jolkinolide B inhibits RANKL-induced osteoclastogenesis by suppressing the activation NF-κB and MAPK signaling pathways.
Osteoclasts together with osteoblasts play pivotal roles in bone remodeling. The unique function and ability of osteoclasts to resorb bone makes them critical in both normal bone homeostasis and pathologic bone diseases such as osteoporosis and rheumatoid arthritis. Thus, new compounds that may inhibit osteoclastogenesis and osteoclast function may be of great value in the treatment of osteoclast-related diseases. In the present study, we examined the effect of jolkinolide B (JB), isolated from the root of Euphorbia fischeriana Steud on receptor activator of NF-κB ligand (RANKL)-induced osteoclast formation. We found that JB inhibited RANKL-induced osteoclast differentiation from bone marrow macrophages (BMMs) without cytotoxicity. Furthermore, the expression of osteoclastic marker genes, such as tartrate-resistant acid phosphatase (TRAP), cathepsin K (CtsK), and calcitonin receptor (CTR), was significantly inhibited. JB inhibited RANKL-induced activation of NF-κB by suppressing RANKL-mediated IκBα degradation. Moreover, JB inhibited RANKL-induced phosphorylation of mitogen-activated protein kinases (p38, JNK, and ERK). This study thus identifies JB as an inhibitor of osteoclast formation and provides evidence that JB might be an alternative medicine for preventing and treating osteolysis.
Department of Orthopaedics, Affiliated Zhongshan Hospital of Dalian University, Dalian 116001, Liaoning Province, People's Republic of China.
Xiaojun
X
Ma
Department of Orthopaedics, Affiliated Zhongshan Hospital of Dalian University, Dalian 116001, Liaoning Province, People's Republic of China.
Yupeng
Y
Liu
Department of Orthopaedics, Affiliated Zhongshan Hospital of Dalian University, Dalian 116001, Liaoning Province, People's Republic of China.
Yao
Y
Zhang
Department of Orthopaedics, Affiliated Zhongshan Hospital of Dalian University, Dalian 116001, Liaoning Province, People's Republic of China.
Xiaobing
X
Yu
Department of Orthopaedics, Affiliated Zhongshan Hospital of Dalian University, Dalian 116001, Liaoning Province, People's Republic of China. Electronic address: oldpal@126.com.
Weiming
W
Wang
Department of Orthopaedics, Affiliated Zhongshan Hospital of Dalian University, Dalian 116001, Liaoning Province, People's Republic of China. Electronic address: ZhaoDW0058@126.com.
Dewei
D
Zhao
D000818:Animals; D001862:Bone Resorption / Q000188:drug therapy / Q000276:immunology; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D004224:Diterpenes / Q000302:isolation & purification / Q000494:pharmacology*; D004365:Drugs, Chinese Herbal / Q000302:isolation & purification / Q000494:pharmacology*; D028481:Euphorbia / Q000737:chemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000276:immunology*; D010010:Osteoclasts / Q000166:cytology / Q000187:drug effects*; D053245:RANK Ligand / Q000276:immunology*; D015398:Signal Transduction / Q000187:drug effects
D004224:Diterpenes; D004365:Drugs, Chinese Herbal; D016328:NF-kappa B; D053245:RANK Ligand; C057914:jolkinolide B
Bone resorption; Jolkinolide B; MAPKs; NF-κB; Osteoclast