Mangiferin attenuates osteoclastogenesis, bone resorption, and RANKL-induced activation of NF-κB and ERK.
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.
Ang
Estabelle
E
School of Surgery, The University of Western Australia, Nedlands, Western Australia 6009, Australia.
Liu
Qian
Q
Qi
Ming
M
Liu
Hua G
HG
Yang
Xiaohong
X
Chen
Honghui
H
Zheng
Ming H
MH
Xu
Jiake
J
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
D016328:NF-kappa B; D053245:RANK Ligand; D044004:Xanthones; C013592:mangiferin; D019892:eIF-2 Kinase; D048049:Extracellular Signal-Regulated MAP Kinases