Deepak, VishwaKasonga, Abe E.Kruger, Marlena C.Coetzee, Magdalena2015-06-252015-06-252015-06Deepak, V, Kasonga, A, Kruger, MC & Coetzee, M 2015, 'Inhibitory effects of eugenol on RANKL-induced osteoclast formation via attenuation of NF-kappa B and MAPK pathways', Connective Tissue Research, vol. 56, no. 3, pp. 195-203.0300-8207 (print)1607-8438 (online)10.3109/03008207.2014.989320http://hdl.handle.net/2263/45782Bone 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.en© Informa Healthcare. This is an electronic version of an article published in Connective Tissue Research, vol. 56, no. 3, pp. 195-203, 2015. doi : 10.3109/03008207.2014.989320. Connective Tissue Research is available online at : http://informahealthcare.com/journal/ctsEugenolRAW264.7 macrophagesOsteoclastRANKLNFκB pathwayMAPK pathwayReceptor activator of NF-κB ligand (RANKL)Mitogen-activated protein kinase pathways (MAPK)Postprint Article