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

Life Sci. 2017 Apr 1;174:15-20. doi: 10.1016/j.lfs.2017.03.002. Epub 2017 Mar 3.

Abstract

Aims: β-Carotene is a natural anti-oxidant, which has been used for treatment of cancer and cardiovascular diseases. Recently, the ameliorating function of β-carotene in osteoporosis has been implicated. However, the precise mechanism of β-carotene in prevention and treatment of osteoporosis is largely unknown. In the present study, we aimed to elucidate how β-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 0.6μM β-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-ĸB) and mitogen-activated protein kinases (MAPK) pathways were evaluated with western blot after BMM cells were exposed to RANKL and β-carotene. The effects of β-carotene in nuclear factor of activated T-cells cytoplasmic 1 (NFATc1), c-Fos and cathepsin K (CTSK) expression were also evaluated.

Key findings: β-Carotene significantly inhibited BMM viability and promoted LDH release at concentrations of 0.4 and 0.6μM. A decrease in RANKL-induced osteoclastogenesis and resorption was also observed after β-carotene treatment. β-Carotene attenuated the NF-ĸB pathway activation by RANKL, with no effect on MAPK pathway. β-Carotene suppressed the upregulation of NFATc1 and c-Fos by RANKL.

Significance: We clarified the anti-osteoclastogenic role of β-carotene, which is mediated by NF-κB signaling.

Keywords: Anti-oxidant; Bone resorption; NF-κB; Osteoclastogenesis; β-Carotene.

MeSH terms

  • Animals
  • Blotting, Western
  • Bone Resorption / prevention & control*
  • Cell Differentiation
  • Cell Survival / drug effects
  • Cells, Cultured
  • Macrophages / cytology*
  • Macrophages / drug effects
  • Macrophages / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Monocytes / cytology*
  • Monocytes / drug effects
  • Monocytes / metabolism
  • NF-kappa B / antagonists & inhibitors*
  • NF-kappa B / metabolism
  • Osteoclasts / cytology*
  • Osteoclasts / drug effects
  • Osteoclasts / metabolism
  • Osteogenesis / drug effects*
  • Osteogenesis / physiology
  • Provitamins / pharmacology
  • Signal Transduction
  • beta Carotene / pharmacology*

Substances

  • NF-kappa B
  • Provitamins
  • beta Carotene