title: Inhibitory effects of eugenol on RANKL-induced osteoclast formation via attenuation of NF-κB and MAPK pathways.
abstract: Bone loss diseases are often associated with increased receptor activator of NF-κB ligand (RANKL)-induced osteoclast formation. Compounds that can attenuate RANKL-mediated osteoclast formation are of great biomedical interest. Eugenol, a phenolic constituent of clove oil possesses medicinal properties; however, its anti-osteoclastogenic potential is unexplored hitherto. Here, we found that eugenol dose-dependently inhibited the RANKL-induced multinucleated osteoclast formation and TRAP activity in RAW264.7 macrophages. The underlying molecular mechanisms included the attenuation of RANKL-mediated degradation of IκBα and subsequent activation of NF-κB pathway. Furthermore, increase in phosphorylation and activation of RANKL-induced mitogen-activated protein kinase pathways (MAPK) was perturbed by eugenol. RANKL-induced expression of osteoclast-specific marker genes such as TRAP, cathepsin K (CtsK) and matrix metalloproteinase-9 (MMP-9) was remarkably downregulated by eugenol. These findings provide the first line of evidence that eugenol mediated attenuation of RANKL-induced NF-κB and MAPK pathways could synergistically contribute to the inhibition of osteoclast formation. Eugenol could be developed as therapeutic agent against diseases with excessive osteoclast activity.
authors.affiliation: Department of Physiology, University of Pretoria , Pretoria , South Africa .
authors.forename: Vishwa
authors.initials: V
authors.lastname: Deepak
authors.forename: Abe
authors.initials: A
authors.lastname: Kasonga
authors.forename: Marlena C
authors.initials: MC
authors.lastname: Kruger
authors.forename: Magdalena
authors.initials: M
authors.lastname: Coetzee
mesh_terms: D000818:Animals; D001862:Bone Resorption / Q000188:drug therapy / Q000235:genetics; D002454:Cell Differentiation / Q000187:drug effects; D005054:Eugenol / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000502:physiology*; D008264:Macrophages / Q000187:drug effects*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D010010:Osteoclasts / Q000166:cytology / Q000187:drug effects*; D053245:RANK Ligand / Q000378:metabolism*; D053246:Receptor Activator of Nuclear Factor-kappa B / Q000378:metabolism
chemical_list: D016328:NF-kappa B; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D005054:Eugenol; D020928:Mitogen-Activated Protein Kinases
keywords: Eugenol; MAPK pathway; NFκB pathway; RANKL; RAW264.7 macrophages; osteoclast