title: 17-Hydroxy-jolkinolide A inhibits osteoclast differentiation through suppressing the activation of NF-κB and MAPKs.
abstract: Osteoclasts (OC) are bone-specific multinucleated giant cells (MNCs) derived from the monocyte/macrophage hematopoietic lineage cells. Inhibiting osteoclast formation is considered as an effective therapeutic approach for the treatment of the pathological bone loss. In this study, we investigated effects of 17-hydroxy-jolkinolide A (HJA), an ent-abietane diterpenoid isolated from the dried root of Euphorbia fischeriana, on osteoclastogenesis induced by RANKL. The results showed that HJA significantly inhibited RANKL-induced osteoclast formation from primary bone marrow macrophages (BMMs). HJA also prevented bone resorption by mature osteoclasts in a dose-dependent manner. In addition, the expression of osteoclastic marker genes, such as tartrate-resistant acid phosphatase (TRAP), cathepsin K (Cts K) and MMP-9, was significantly inhibited by HJA. Furthermore, HJA also significantly inhibited RANKL-induced activation of NF-κB and phosphorylation of MAPK. Our results indicate that HJA has an inhibitory role in the bone loss by preventing osteoclast formation as well as its bone resorptive activity. Therefore, HJA may be useful as a therapeutic reagent for bone loss-associated diseases.
authors.affiliation: Key Laboratory of Zoonosis, Ministry of Education, Institute of Zoonosis, Jilin University, Changchun 130062, PR China; Department of Gynaecology and Obstetrics, China-Japan Union Hospital, Jilin University, Changchun 130033, PR China.
authors.forename: Yingjian
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Key Laboratory of Zoonosis, Ministry of Education, Institute of Zoonosis, Jilin University, Changchun 130062, PR China.
authors.forename: Xiaohan
authors.initials: X
authors.lastname: Xu
authors.affiliation: School of Life Sciences and Technology, Tongji University, Shanghai 200092, PR China.
authors.forename: Hong-Bing
authors.initials: HB
authors.lastname: Wang
authors.affiliation: Jilin Provincial Center for Disease Control and Prevention, 130062, PR China.
authors.forename: Donglin
authors.initials: D
authors.lastname: Wu
authors.affiliation: Clinical Laboratory, Tumor Hospital of Jilin Province, Changchun 130022, PR China.
authors.forename: Xiao-Ou
authors.initials: XO
authors.lastname: Li
authors.affiliation: Key Laboratory of Zoonosis, Ministry of Education, Institute of Zoonosis, Jilin University, Changchun 130062, PR China.
authors.forename: Qisheng
authors.initials: Q
authors.lastname: Peng
authors.affiliation: Central Laboratory, The Second Clinical Hospital, Jilin University, Changchun 130041, PR China. Electronic address: liu_ning@jlu.edu.cn.
authors.forename: Ning
authors.initials: N
authors.lastname: Liu
authors.affiliation: Key Laboratory of Zoonosis, Ministry of Education, Institute of Zoonosis, Jilin University, Changchun 130062, PR China. Electronic address: wanchunsun@jlu.edu.cn.
authors.forename: Wan-Chun
authors.initials: WC
authors.lastname: Sun
mesh_terms: D000818:Animals; D001862:Bone Resorption / Q000473:pathology; D002454:Cell Differentiation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004224:Diterpenes / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors*; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D010010:Osteoclasts / Q000187:drug effects*; D053245:RANK Ligand / Q000096:biosynthesis / Q000235:genetics
chemical_list: D004224:Diterpenes; D004791:Enzyme Inhibitors; D016328:NF-kappa B; D053245:RANK Ligand; C505689:Tnfsf11 protein, mouse; C057915:jolkinolide A; D020928:Mitogen-Activated Protein Kinases
keywords: 17-Hydroxy-jolkinolide A; Bone resorption; MAPK; NF-κB; Osteoclast; RANKL