Vitamin K catabolite inhibition of ovariectomy‐induced bone loss: Structure–activity relationship considerations. Issue 8 (14th July 2014)

• Record Type: Journal Article
• Authors: Soper, Robin J.; Oguz, Cenk; Emery, Roger; Pitsillides, Andrew A.; Hodges, Stephen J.; Traber, Maret G.
• Is Part Of: Molecular nutrition & food research. Volume 58:Issue 8(2014:Aug.)
• Page Start: 1658
• Page End: 1666
• Publication Date: 2014-07-14
• Subjects: Food -- Biotechnology -- Periodicals; Food -- Microbiology -- Periodicals; Nutrition -- Periodicals; Food -- Toxicology -- Periodicals; Nutrition -- Periodicals; Food Microbiology -- Periodicals; Food Technology -- Periodicals; Molecular Biology -- Periodicals; 664.0705
• DOI: 10.1002/mnfr.201400063
• Languages: English
• ISSNs: 1613-4125

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="mnfr2224-sec-0010" sec-type="section"> <title>Scope</title> <p>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.</p> </sec> <sec id="mnfr2224-sec-0020" sec-type="section"> <title>Methods and results</title> <p>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.</p> </sec> <sec id="mnfr2224-sec-0030" sec-type="section"> <title>Conclusion</title> <p>These in vivo data indicate for the first time that the clinical utility of vitamin K for osteoporosis may reside in an unusual catabolite.</p> </sec> </abstract>