Natural Germacrane Sesquiterpenes Inhibit Osteoclast Formation, Bone Resorption, RANKL-Induced NF-B Activation, and IB Degradation

S. Qin, Estabelle Ang, L. Dai, X. Yang, Dongping Ye, H. Chen, L. Zhou, M. Yang, D.A. Teguh, R. Tan, J. Xu, Jennifer Tickner, Nathan Pavlos, Jiake Xu

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Abstract

Osteolytic bone diseases are commonly presented with enhanced osteoclast formation and bone resorption. Sesquiterpene lactone natural compounds have been found to possess anti-inflammatory and immune-modulation effects. Here, we identified three germacrane sesquiterpenes using computer-based virtual screening for the structural similarity with sesquiterpene lactone, parthenolide. We showed that natural germacrane sesquiterpene compounds A, B, and C inhibit osteoclast formation and bone resorption in a dose-dependent manner, with relative potency compound A > compound C > compound B based on their equimolar concentrations. Mechanistic studies by Luciferase reporter gene assay and Western blot analysis showed that germacrane sesquiterpene compound A inhibits RANKL-induced activation of NF-κB and IκBα degradation. This study reveals that natural germacrane sesquiterpene compounds are inhibitors for osteoclast formation and bone resorption, and provides evidence that naturally-occurring compounds might be beneficial as alternative medicine for the prevention and treatment of osteolysis.
Original languageEnglish
Pages (from-to)26599–26607
Number of pages9
JournalInternational Journal of Molecular Sciences
Volume16
Issue number11
DOIs
Publication statusPublished - 5 Nov 2015

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