The inhibitory effect of vitamin K on RANKL-induced osteoclast differentiation and bone resorption.
To further understand the correlation between vitamin K and bone metabolism, the effects of vitamins K1, menaquinone-4 (MK-4), and menaquinone-7 (MK-7) on RANKL-induced osteoclast differentiation and bone resorption were comparatively investigated. Vitamin K2 groups (MK-4 and MK-7) were found to significantly inhibit RANKL-medicated osteoclast cell formation of bone marrow macrophages (BMMs) in a dose-dependent manner, without any evidence of cytotoxicity. The mRNA expression of specific osteoclast differentiation markers, such as c-Fos, NFATc1, OSCAR, and TRAP, as well as NFATc1 protein expression and TRAP activity in RANKL-treated BMMs were inhibited by vitamin K2, although MK-4 exhibited a significantly greater efficiency compared to MK-7. In contrast, the same dose of vitamin K1 had no inhibitory effect on RANKL-induced osteoclast cell formation, but increased the expression of major osteoclastogenic genes. Interestingly, vitamins K1, MK-4 and MK-7 all strongly inhibited osteoclastic bone resorption (p < 0.01) in a dose dependent manner. These results suggest that vitamins K1, MK-4 and MK-7 have anti-osteoporotic properties, while their regulation effects on osteoclastogenesis are somewhat different.
Institute of food science, Zhejiang Academy of Agricultural Sciences, Hangzhou, Zhejiang 310021, PR China.
Wei-Jie
WJ
Wu
Min Seuk
MS
Kim
Byung-Yong
BY
Ahn
D000135:Acid Phosphatase / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects / Q000378:metabolism; D001862:Bone Resorption / Q000188:drug therapy*; D002454:Cell Differentiation / Q000187:drug effects*; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D050778:NFATC Transcription Factors / Q000235:genetics / Q000378:metabolism; D010010:Osteoclasts / Q000187:drug effects* / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism; D053245:RANK Ligand / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D000071681:Tartrate-Resistant Acid Phosphatase; D014812:Vitamin K / Q000031:analogs & derivatives / Q000494:pharmacology*; D010837:Vitamin K 1 / Q000494:pharmacology; D024482:Vitamin K 2 / Q000031:analogs & derivatives / Q000494:pharmacology
D007527:Isoenzymes; D050778:NFATC Transcription Factors; C494005:Nfatc1 protein, mouse; C450519:Oscar protein, mouse; D016760:Proto-Oncogene Proteins c-fos; D053245:RANK Ligand; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; C505689:Tnfsf11 protein, mouse; D024482:Vitamin K 2; D014812:Vitamin K; C030814:menatetrenone; D010837:Vitamin K 1; C062629:menaquinone 7; D000135:Acid Phosphatase; C000605511:Acp5 protein, mouse; D000071681:Tartrate-Resistant Acid Phosphatase