Carvacrol inhibits osteoclastogenesis and negatively regulates the survival of mature osteoclasts

Show simple item record Deepak, Vishwa Kasonga, Abe E. Kruger, Marlena C. Coetzee, Magdalena 2016-08-05T10:03:28Z 2016-08-05T10:03:28Z 2016-07
dc.description.abstract Bone is a dynamic tissue that undergoes continuous remodeling coupled with the action of osteoblasts and osteoclasts. Osteoclast activity is elevated during osteoporosis and periodontitis resulting in excessive loss of trabecular and alveolar bone. Osteoclasts are formed in an inflammatory response to cytokine production receptor activator of nuclear factor-kappaB (NF-κB) ligand (RANKL) and bacterial challenge lipopolysaccharide (LPS). Carvacrol, a monoterpenic phenol present in Origanum vulgare and Thymus vulgaris, is a natural compound with known medicinal properties. We investigated the effects of carvacrol on osteoclast formation induced by RANKL and LPS. Carvacrol suppressed RANKL-induced formation of tartrate resistant acid phosphatase (TRAP)-positive multinucleated cells in RAW264.7 macrophages and human CD14 monocytes. Furthermore, carvacrol inhibited LPS-induced osteoclast formation in RAW264.7 macrophages. Investigation of the underlying molecular mechanisms revealed that carvacrol downregulated RANKL-induced NF-κB activation in a dose-dependent manner. Furthermore, the suppression of NF-κB activation correlated with inhibition of inhibitor of kappaB (IκB) kinase (IKK) activation and attenuation of inhibitor of NF-κB (IκBa) degradation. Carvacrol potentiated apoptosis in mature osteoclasts by caspase-3 activation and DNA fragmentation. Moreover, carvacrol did not affect the viability of proliferating MC3T3- E1 osteoblast-like cells. Collectively, these results demonstrate that carvacrol mitigates osteoclastogenesis by impairing the NF-κB pathway and induction of apoptosis in mature osteoclasts. en_ZA
dc.description.department Human Nutrition en_ZA
dc.description.department Physiology en_ZA
dc.description.librarian am2016 en_ZA
dc.description.sponsorship RESCOM, University of Pretoria; the University of Pretoria Vice Chancellor’s Postdoctoral Research Fellowship; the University of Pretoria’s Strategic Institutional Research Theme in Food, Nutrition and Well-being; and in part by the Struwig- Germeshuysen Cancer Research Trust, South Africa. en_ZA
dc.description.uri en_ZA
dc.identifier.citation Deepak, V, Kasonga, A, Kruger, MC & Coetzee, M 2016, 'Carvacrol inhibits osteoclastogenesis and negatively regulates the survival of mature osteoclasts', Biological and Pharmaceutical Bulletin, vol. 39, no. 7, pp. 1150-1158. en_ZA
dc.identifier.issn 0918-6158 (print)
dc.identifier.issn 1347-5215 (online)
dc.language.iso en en_ZA
dc.publisher Pharmaceutical Society of Japan en_ZA
dc.rights © 2016 The Pharmaceutical Society of Japan en_ZA
dc.subject Osteoclast en_ZA
dc.subject Osteoporosis en_ZA
dc.subject Periodontitis en_ZA
dc.subject Receptor activator of nuclear factor-κB ligand (RANKL) en_ZA
dc.subject Lipopolysaccharide (LPS) en_ZA
dc.subject Nuclear factor-kappaB (NF-κB) en_ZA
dc.title Carvacrol inhibits osteoclastogenesis and negatively regulates the survival of mature osteoclasts en_ZA
dc.type Article en_ZA

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