Effect of Menaquinone-4 on Receptor Activator of Nuclear Factor κ B Ligand-Induced Osteoclast Differentiation and Ovariectomy-Induced Bone Loss

J Med Food. 2023 Feb;26(2):128-134. doi: 10.1089/jmf.2022.K.0078. Epub 2023 Feb 1.

Abstract

Osteoporosis is a progressive metabolic disease characterized by decreased bone mineral density and increased fracture risk. Previous studies have shown that higher intake of vitamin K (VK) correlates with a reduced risk of osteoporosis. However, the effect of menaquinone-4 (MK-4), a specific form of VK, still remains obscure. Therefore, in this study, we investigated the effects of MK-4 on osteoclast differentiation by differentiating RAW 264.7 cells into osteoclasts with the help of receptor activator of nuclear factor-kappa B ligand (RANKL), assessed the mRNA expression of osteoclast-specific genes, and studied the effects of MK-4 in vivo in ovariectomized mice, a postmenopausal osteoporosis murine model. MK-4 inhibited osteoclast differentiation, decreased the mRNA expression of nuclear factor of activated T cells c1 (NFATc1), osteoclast-associated receptor (OSCAR), and cathepsin K (CTSK), and inhibited bone loss in ovariectomized mice. The findings strongly suggest that MK-4 is a therapeutic alternative for postmenopausal osteoporosis.

Keywords: gene expression; menaquinone-4; microcomputed tomography; osteoclast; postmenopausal osteoporosis.

MeSH terms

  • Animals
  • Bone Resorption* / drug therapy
  • Bone Resorption* / genetics
  • Bone Resorption* / metabolism
  • Cell Differentiation
  • Female
  • Humans
  • Mice
  • NF-kappa B / metabolism
  • Osteoclasts
  • Osteogenesis
  • Osteoporosis* / drug therapy
  • Osteoporosis* / etiology
  • Osteoporosis* / metabolism
  • Osteoporosis, Postmenopausal* / drug therapy
  • Ovariectomy / adverse effects
  • RANK Ligand / metabolism
  • RNA, Messenger / metabolism

Substances

  • NF-kappa B
  • RANK Ligand
  • menatetrenone
  • RNA, Messenger