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Uncarboxylated Osteocalcin Increases Serum Nitric Oxide Levels and Ameliorates Hypercholesterolemia in Mice Fed an Atherogenic Diet

Background: Osteocalcin (OC), an osteoblastderived bone matrix protein, may be involved in atherosclerosis pathophysiology. The physiological action of OC and the effect of OC administration under atherogenic conditions in vivo have not yet been examined.

Methods and findings: Here we demonstrate that acute or Chronic Uncarboxylated OC (GluOC) injection in wild-type C57BL/6 female mice fed a normal diet or a diet supplemented with cholesterol and cholic acid resulted in increased serum Nitric Oxide (NO) levels. Furthermore, our study shows that GluOC treatment led to elevated expression levels of liver X receptor α (LXRα), a key transcription factor in cholesterol metabolism, in white adipose tissue and liver and ameliorated hypercholesteromia in those mice.

Conclusion: We thus propose that GluOC exhibited potential atheroprotective effects through serum NO production and hypercholesterolemia improvement in wild-type mice.


Akihiko Kondo, Tomoyo Kawakubo-Yasukochi, Akiko Mizokami, Sakura Chishaki, Hiroshi Takeuchi, Masato Hirata

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