Vitamin K catabolite inhibition of ovariectomy-induced bone loss: Structure–activity relationship considerations
Version of Record online: 14 JUL 2014
© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Molecular Nutrition & Food Research
Special Issue: Vitamin K Conundrums
Volume 58, Issue 8, pages 1658–1666, August 2014
How to Cite
Soper, R. J., Oguz, C., Emery, R., Pitsillides, A. A. and Hodges, S. J. (2014), Vitamin K catabolite inhibition of ovariectomy-induced bone loss: Structure–activity relationship considerations. Mol. Nutr. Food Res., 58: 1658–1666. doi: 10.1002/mnfr.201400063
- Issue online: 4 AUG 2014
- Version of Record online: 14 JUL 2014
- Manuscript Accepted: 3 JUN 2014
- Manuscript Revised: 31 MAY 2014
- Manuscript Received: 28 JAN 2014
- Heptagon Fund
- Bone loss;
- Vitamin K
The potential benefit of vitamin K as a therapeutic in osteoporosis is controversial and the vitamin K regimen being used clinically (45 mg/day) employs doses that are many times higher than required to ensure maximal gamma-carboxylation of the vitamin K-dependent bone proteins. We therefore tested the hypothesis that vitamin K catabolites, 5-carbon (CAN5C) and 7-carbon carboxylic acid (CAN7C) aliphatic side-chain derivatives of the naphthoquinone moiety exert an osteotrophic role consistent with the treatment of osteoporosis.
Methods and results
Osteoblast-like MG63 cell cultures were challenged with lipopolysaccharide and the levels of interleukin-6, an osteoclastogenic cytokine, measured with and without catabolites; low concentrations of CAN7C significantly inhibited interleukin-6 release, but CAN5C did not. In models of bone loss induced by ovariectomy or sciatic neurectomy in C57BL/6 mice, we found that the rarer CAN7C catabolite markedly restricted ovariectomy-induced bone loss and possibly limited sciatic neurectomy-induced bone loss. CAN7C activity depends on a free carboxylic acid and its particular side-chain structure.
These in vivo data indicate for the first time that the clinical utility of vitamin K for osteoporosis may reside in an unusual catabolite.