β-Carotene suppresses osteoclastogenesis and bone resorption by suppressing NF-κB signaling pathway

Aims: beta-Carotene is a natural anti-oxidant, which has been used for treatment of cancer and cardiovascular diseases. Recently, the ameliorating function of beta-carotene in osteoporosis has been implicated. However, the precise mechanism of beta-carotene in prevention and treatment of osteoporosis is largely unknown. In the present study, we aimed to elucidate how beta-carotene affects osteoclast formation and bone resorption. Main methods: Bone marrow-derived monocytes/-macrophages (BMM) were exposed to 0.05, 0.1, 0.2, 0.4 and 0.6 mu M beta-carotene, followed by evaluation of cell viability, lactate dehydrogenase (LDH) release, receptor activator of nuclear factor kappa B ligand (RANKL)-induced osteoclastogenesis and resorption pits formation. Key factors in nuclear factor kappa B (NF-kappa B) and mitogen-activated protein kinases (MAPK) pathways were evaluated with western blot after BMM cells were exposed to RANKL and beta-carotene. The effects of beta-carotene in nuclear factor of activated T-cells cytoplasmic 1 (NFATc1), c-Fos and cathepsin K (CTSK) expression were also evaluated. Key findings: beta-Carotene significantly inhibited BMM viability and promoted LDH release at concentrations of 0.4 and 0.6 mu M. A decrease in RANKL-induced osteoclastogenesis and resorption was also observed after beta-carotene treatment. beta-Carotene attenuated the NF-kappa B pathway activation by RANKL, with no effect on MAPK pathway. beta-Carotene suppressed the upregulation of NFATc1 and c-Fos by RANKL. Significance: We clarified the anti-osteoclastogenic role of beta-carotene, which is mediated by NF-kappa B signaling. (C) 2017 Elsevier Inc. All rights reserved.