title: Calycosin Suppresses RANKL-Mediated Osteoclastogenesis through Inhibition of MAPKs and NF-κB.
abstract: Calycosin, an isoflavonoid phytoestrogen, isolated from Radix Astragali, was reported to possess anti-tumor, anti-inflammation, and osteogenic properties, but its impact on osteoclast differentiation remains unclear. In this study, we examined the effects of calycosin on osteoclastogenesis induced by RANKL. The results showed that calycosin significantly inhibited RANKL-induced osteoclast formation from primary bone marrow macrophages (BMMs). Calycosin also dose-dependently suppressed the formation of bone resorption pits by mature osteoclasts. In addition, the expression of osteoclatogenesis-related genes, including cathepsin K (CtsK), tartrate-resistant acid phosphatase (TRAP), and MMP-9, was significantly inhibited by calycosin. Furthermore, the results indicated that calycosin down-regulated the expression levels of NFATc1 and c-Fos through suppressing the activation of NF-κB and MAPKs. Our results indicate that calycosin has an inhibitory role in the bone loss by preventing osteoclast formation, as well as its bone resorptive activity. Therefore, calycosin may be useful as a therapeutic reagent for bone loss-associated diseases.
authors.affiliation: Key Laboratory for Molecular and Chemical Genetics of Critical Human Diseases of Jilin Province, Jilin University Bethune Second Hospital, Changchun 130041, China. qgh0521@jlu.edu.cn.
authors.forename: Gui-Hua
authors.initials: GH
authors.lastname: Quan
authors.affiliation: School of Life Sciences and Technology, Tongji University, Shanghai 200092, China. hbwang@tongji.edu.cn.
authors.forename: Hongbing
authors.initials: H
authors.lastname: Wang
authors.affiliation: Key laboratory of Zoonosis, Ministry of Education, Institute of Zoonosis, Jilin University, Changchun 130062, China. jinjincao90@163.com.
authors.forename: Jinjin
authors.initials: J
authors.lastname: Cao
authors.affiliation: Key laboratory of Zoonosis, Ministry of Education, Institute of Zoonosis, Jilin University, Changchun 130062, China. chongfengxing@163.com.
authors.forename: Yuxin
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Virus Disease Prevention and Control, Jilin Provincial Center for Disease Control and Prevention, Changchun 130062, China. dl_wu@163.com.
authors.forename: Donglin
authors.initials: D
authors.lastname: Wu
authors.affiliation: Key laboratory of Zoonosis, Ministry of Education, Institute of Zoonosis, Jilin University, Changchun 130062, China. pengqs@jlu.edu.cn.
authors.forename: Qisheng
authors.initials: Q
authors.lastname: Peng
authors.affiliation: Key Laboratory for Molecular and Chemical Genetics of Critical Human Diseases of Jilin Province, Jilin University Bethune Second Hospital, Changchun 130041, China. 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, China. wanchunsun@jlu.edu.cn.
authors.forename: Wan-Chun
authors.initials: WC
authors.lastname: Sun
mesh_terms: D000818:Animals; D001862:Bone Resorption; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D015870:Gene Expression; D007529:Isoflavones / Q000494:pharmacology*; D020935:MAP Kinase Signaling System; D008264:Macrophages / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D050778:NFATC Transcription Factors / Q000235:genetics / Q000378:metabolism; D010010:Osteoclasts / Q000187:drug effects / Q000502:physiology*; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism; D053245:RANK Ligand / Q000502:physiology*; D015533:Transcriptional Activation
chemical_list: D007529:Isoflavones; D016328:NF-kappa B; D050778:NFATC Transcription Factors; C494005:Nfatc1 protein, mouse; D016760:Proto-Oncogene Proteins c-fos; D053245:RANK Ligand; C505689:Tnfsf11 protein, mouse; C121707:7,3'-dihydroxy-4'-methoxyisoflavone; D020928:Mitogen-Activated Protein Kinases
keywords: MAPKs; NF-κB; NFATc1; bone resorption; c-Fos; calycosin; osteoclast