Bone loss is associated with a wide array of diseases such as osteoporosis, cancer and chronic periodontitis. One of the common factors observed among these diseases involves elevated osteoclast activity. Selective targeting of osteoclast formation is an effective approach to exacerbate bone loss. In this study, we investigated the effects of carvacrol, a monoterpenic phenol present in the essential oils of Origanum vulgare, Thymus vulgaris and Carum copticum on osteoclast formation and activity. The effects of carvacrol on osteoclastogenesis was assessed by analysing the following: cell viability, TRAP+ multinucleated osteoclast formation, actin ring formation, bone resorption and nuclear fragmentation assay. We found that treatment of RAW264.7 macrophages and human CD14+ monocytes with carvacrol suppressed RANKL-induced osteoclast formation in a dose-dependent manner without cytotoxicity. Carvacrol also inhibited the bacterial lipopolysaccharide (LPS)-induced osteoclast formation in RAW264.7 macrophages. Moreover, treatment of RAW264.7 macrophages with conditioned-media derived from MDA-MB-231 and MCF-7 human breast cancer cells resulted in osteoclast formation which was further perturbed by carvacrol. Carvacrol disrupted actin ring formation and bone resorptive function of osteoclasts. Intriguingly, exposure of mature osteoclasts to carvacrol lead to a reduction in osteoclast numbers. These cells showed nuclear fragmentation and condensation, a characteristic hallmark of apoptosis. Additionally, carvacrol did not decrease cell viability of MC3T3-E1 osteoblast like cells. Together, these results suggest that carvacrol effectively blocks osteoclastogenesis induced under various pathophysiological stimuli and could be developed as a therapeutic agent.
Disclosure: The authors declared no competing interests. This study was supported by grants from RESCOM, University of Pretoria; the University of Pretoria Vice Chancellors Postdoctoral Research Fellowship; the University of Pretorias Strategic Institutional Research Theme in Food, Nutrition and Well-Being and the Struwig-Germeshuysen Kankernavorsingstrust (SGKN TRUST).