What is the function of osteocalcin?

Background: Osteocalcin is the most abundant non-collagenous protein in bone and is specifically expressed in osteoblasts. Previous studies using osteocalcin-deficient (Ocn(-/-)) mice demonstrated that osteocalcin inhibits bone formation, and serum uncarboxylated osteocalcin functions as a hormone that improves glucose metabolism, induces testosterone synthesis in the testes, and maintains muscle mass. Furthermore, the relationship between serum osteocalcin and glucose metabolism or cardiovascular risk in humans has been reported. However, new Ocn(-/-) mice exhibited different phenotypes. Highlight: Bone volume, formation, and resorption were normal in the new Ocn(-/-) mice. The orientation of collagen fibers was parallel to the bone longitudinal direction and the size of apatite crystals was normal, but the c-axis of apatite crystals was random and bone strength was reduced in new Ocn(-/-) mice. Glucose metabolism, testosterone synthesis, and muscle mass were normal in new Ocn(-/-) mice. Exercise improved glucose metabolism and increased bone formation, leading to an increase in the serum osteocalcin level, which is a marker for bone formation. Conclusion: Contrary to previous findings, new Ocn(-/-) mice revealed that osteocalcin has no function in the regulation of bone quantity, but instead, functions to direct the parallel alignment of the c-axis of apatite crystals with collagen fibrils. Moreover, it has no physiological function as a hormone that regulates glucose metabolism, testosterone synthesis, or muscle mass. These controversial phenotypes require further investigation. The relationship of serum osteocalcin with glucose metabolism or cardiovascular risk suggests the importance of exercise for their improvement. (C) 2020 Japanese Association for Oral Biology. Published by Elsevier B.V. All rights reserved.