17-Hydroxy-jolkinolide A inhibits osteoclast differentiation through suppressing the activation of NF-κB and MAPKs

Yingjian Wang; Xiaohan Xu; Hong-Bing Wang; Donglin Wu; Xiao-Ou Li; Qisheng Peng; Ning Liu; Wan-Chun Sun

doi:10.1016/j.intimp.2015.10.004

17-Hydroxy-jolkinolide A inhibits osteoclast differentiation through suppressing the activation of NF-κB and MAPKs

Int Immunopharmacol. 2015 Dec;29(2):513-520. doi: 10.1016/j.intimp.2015.10.004. Epub 2015 Oct 9.

Authors

Yingjian Wang¹, Xiaohan Xu², Hong-Bing Wang³, Donglin Wu⁴, Xiao-Ou Li⁵, Qisheng Peng², Ning Liu⁶, Wan-Chun Sun⁷

Affiliations

¹ 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.
² Key Laboratory of Zoonosis, Ministry of Education, Institute of Zoonosis, Jilin University, Changchun 130062, PR China.
³ School of Life Sciences and Technology, Tongji University, Shanghai 200092, PR China.
⁴ Jilin Provincial Center for Disease Control and Prevention, 130062, PR China.
⁵ Clinical Laboratory, Tumor Hospital of Jilin Province, Changchun 130022, PR China.
⁶ Central Laboratory, The Second Clinical Hospital, Jilin University, Changchun 130041, PR China. Electronic address: [email protected].
⁷ Key Laboratory of Zoonosis, Ministry of Education, Institute of Zoonosis, Jilin University, Changchun 130062, PR China. Electronic address: [email protected].

PMID: 26456501
DOI: 10.1016/j.intimp.2015.10.004

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.

Keywords: 17-Hydroxy-jolkinolide A; Bone resorption; MAPK; NF-κB; Osteoclast; RANKL.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Bone Resorption / pathology
Cell Differentiation / drug effects
Cell Survival / drug effects
Diterpenes / pharmacology*
Enzyme Activation / drug effects
Enzyme Inhibitors / pharmacology*
Gene Expression Regulation, Enzymologic / drug effects
Male
Mice
Mice, Inbred C57BL
Mitogen-Activated Protein Kinases / antagonists & inhibitors*
NF-kappa B / antagonists & inhibitors*
Osteoclasts / drug effects*
RANK Ligand / biosynthesis
RANK Ligand / genetics

Substances

Diterpenes
Enzyme Inhibitors
NF-kappa B
RANK Ligand
Tnfsf11 protein, mouse
jolkinolide A
Mitogen-Activated Protein Kinases