TY - JOUR
T1 - Natural Germacrane Sesquiterpenes Inhibit Osteoclast Formation, Bone Resorption, RANKL-Induced NF-B Activation, and IB Degradation
AU - Qin, S.
AU - Ang, Estabelle
AU - Dai, L.
AU - Yang, X.
AU - Ye, Dongping
AU - Chen, H.
AU - Zhou, L.
AU - Yang, M.
AU - Teguh, D.A.
AU - Tan, R.
AU - Xu, J.
AU - Tickner, Jennifer
AU - Pavlos, Nathan
AU - Xu, Jiake
PY - 2015/11/5
Y1 - 2015/11/5
N2 - 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.
AB - 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.
KW - Animals
KW - Biological Products/pharmacology
KW - Bone Resorption/metabolism
KW - Enzyme Activation/drug effects
KW - I-kappa B Proteins/metabolism
KW - Macrophages
KW - Mice
KW - NF-KappaB Inhibitor alpha
KW - NF-kappa B/metabolism
KW - Osteoclasts/drug effects
KW - Proteolysis/drug effects
KW - RANK Ligand/metabolism
KW - Sesquiterpenes, Germacrane/pharmacology
U2 - 10.3390/ijms161125972
DO - 10.3390/ijms161125972
M3 - Article
C2 - 26556352
SN - 1661-6596
VL - 16
SP - 26599
EP - 26607
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
IS - 11
ER -