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Bone. 2016 Jan;82:42-9. doi: 10.1016/j.bone.2015.05.046. Epub 2015 Jun 6.

New insights into the biology of osteocalcin.

Author information

1
Department of Orthopaedic Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
2
Department of Orthopaedic Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Baltimore Veterans Administration Medical Center, Baltimore, MD, USA.
3
Department of Orthopaedic Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Baltimore Veterans Administration Medical Center, Baltimore, MD, USA. Electronic address: rriddle1@jhmi.edu.

Abstract

Osteocalcin is among the most abundant proteins in bone and is produced exclusively by osteoblasts. Initially believed to be an inhibitor of bone mineralization, recent studies suggest a broader role for osteocalcin that extends to the regulation of whole body metabolism, reproduction, and cognition. Circulating undercarboxylated osteocalcin, which is regulated by insulin, acts in a feed-forward loop to increase β-cell proliferation as well as insulin production and secretion, while skeletal muscle and adipose tissue respond to osteocalcin by increasing their sensitivity to insulin. Osteocalcin also acts in the brain to increase neurotransmitter production and in the testes to stimulate testosterone production. At least one putative receptor for osteocalcin, Gprc6a, is expressed by adipose, skeletal muscle, and the Leydig cells of the testes and appears to mediate osteocalcin's effects in these tissues. In this review, we summarize these new discoveries, which suggest that the ability of osteocalcin to function both locally in bone and as a hormone depends on a novel post-translational mechanism that alters osteocalcin's affinity for the bone matrix and bioavailability. This article is part of a Special Issue entitled Bone and diabetes.

KEYWORDS:

Diabetes; Metabolism; Osteoblast; Osteocalcin

PMID:
26055108
PMCID:
PMC4670816
DOI:
10.1016/j.bone.2015.05.046
[Indexed for MEDLINE]
Free PMC Article

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