title: Mangiferin attenuates osteoclastogenesis, bone resorption, and RANKL-induced activation of NF-κB and ERK.
abstract: Osteolytic bone diseases such as osteoporosis have a common pathological feature in which osteoclastic bone resorption outstrips bone synthesis. Osteoclast formation and activation are regulated by receptor activator of nuclear factor κB ligand (RANKL). The induction of RANKL-signaling pathways occurs following the interaction of RANKL to its cognate receptor, RANK. This specific binding drives the activation of downstream signaling pathways; which ultimately induce the formation and activation of osteoclasts. In this study, we showed that a natural immunomodulator, mangiferin, inhibits osteoclast formation and bone resorption by attenuating RANKL-induced signaling. Mangiferin diminished the expression of osteoclast marker genes, including cathepsin K, calcitonin receptor, DC-STAMP, and V-ATPase d2. Mechanistic studies revealed that mangiferin inhibits RANKL-induced activation of NF-κB, concomitant with the inhibition of IκB-α degradation, and p65 nuclear translocation. In addition, mangiferin also exhibited an inhibitory effect on RANKL-induced ERK phosphorylation. Collectively, our data demonstrates that mangiferin exhibits anti-resorptive properties, suggesting the potential application of mangiferin for the treatment and prevention of bone diseases involving excessive osteoclastic bone resorption.
authors.affiliation: School of Surgery, The University of Western Australia, Nedlands, Western Australia 6009, Australia.
authors.forename: Estabelle
authors.initials: E
authors.lastname: Ang
authors.forename: Qian
authors.initials: Q
authors.lastname: Liu
authors.forename: Ming
authors.initials: M
authors.lastname: Qi
authors.forename: Hua G
authors.initials: HG
authors.lastname: Liu
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Yang
authors.forename: Honghui
authors.initials: H
authors.lastname: Chen
authors.forename: Ming H
authors.initials: MH
authors.lastname: Zheng
authors.forename: Jiake
authors.initials: J
authors.lastname: Xu
mesh_terms: D000818:Animals; D001847:Bone Diseases / Q000378:metabolism / Q000517:prevention & control; D001862:Bone Resorption / Q000378:metabolism*; D002454:Cell Differentiation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D006801:Humans; D051379:Mice; D018613:Microscopy, Confocal; D016328:NF-kappa B / Q000378:metabolism*; D010010:Osteoclasts / Q000187:drug effects* / Q000378:metabolism; D053245:RANK Ligand / Q000378:metabolism*; D015398:Signal Transduction; D044004:Xanthones / Q000494:pharmacology*; D019892:eIF-2 Kinase / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D016328:NF-kappa B; D053245:RANK Ligand; D044004:Xanthones; C013592:mangiferin; D019892:eIF-2 Kinase; D048049:Extracellular Signal-Regulated MAP Kinases