Osteocalcin: Skeletal and extra‐skeletal effects

Neve, Anna; Corrado, Addolorata; Cantatore, Francesco Paolo

doi:10.1002/jcp.24278

Cited by 335Bone Metabolism and DiseasesBone and Dental Protein StudiesAlkaline Phosphatase Research Studies

Osteocalcin: Skeletal and extra‐skeletal effects

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Neve, Anna, Corrado, Addolorata, Cantatore, Francesco Paolo·2013·Journal of Cellular Physiology

DOI 10.1002/jcp.24278

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Abstract

Osteocalcin (OC) is a non‐collagenous, vitamin K‐dependent protein secreted in the late stage of osteoblasts differentiation. The presence of the three residues of γ‐carbossiglutamatic acid, specific of the active form of OC protein, allows the protein to bind calcium and consequently hydroxyapatite. The osteoblastic OC protein is encoded by the bone γ‐carbossiglutamate gene whose transcription is principally regulated by the Runx2/Cbfa1 regulatory element and stimulated by vitamin D 3 through a steroid‐responsive enhancer sequence. Even if data obtained in literature are controversial, the dual role of OC in bone can be presumed as follows: firstly, OC acts as a regulator of bone mineralization; secondly, OC regulates osteoblast and osteoclast activity. Recently the metabolic activity of OC, restricted to the un‐carboxylated form has been demonstrated in osteoblast‐specific knockout mice. This effect is mediated by the regulation of pancreatic β‐cell proliferation and insulin secretion and adiponectin production by adipose tissue and leads to the regulation of glucose metabolism and fat mass. Nevertheless, clinical human studies only demonstrated the correlation between OC levels and factors related to energy metabolism. Thus further investigations in humans are required to demonstrate the role of OC in the regulation of human energy metabolism. Moreover, it is presumable that OC also acts on blood vessels by inducing angiogenesis and pathological mineralization. This review highlights the recent studies concerning skeletal and extra‐skeletal effects of OC. J. Cell. Physiol. 228: 1149–1153, 2013. © 2012 Wiley Periodicals, Inc.

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Osteocalcin supports insulin function and thus storage of energy-rich fuels in adipose tissue and muscle.
“Nevertheless, these studies indicate that osteocalcin supports insulin function and thus storage of energy-rich fuels in adipose tissue and muscle.”
From Interaction of the endocrine system with inflammation: a function of energy and volume regulation (2014) · cites this paper as [31]

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“Osteocalcin is an osteoblast hormone that can bind calcium ions, regulates bone mineralization and bone turnover, and is used as a biomarker for bone formation [31].”
Background
The Development of Molecular Biology of Osteoporosis
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Protein Biomarkers of Periodontitis in Saliva
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Vitamin K and bone
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A Biomimetic Biphasic Osteochondral Scaffold with Layer‐Specific Release of Stem Cell Differentiation Inducers for the Reconstruction of Osteochondral Defects
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IGF1 promotes osteogenic differentiation of mesenchymal stem cells derived from rat bone marrow by increasing TAZ expression
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Octacalcium phosphate – a metastable mineral phase controls the evolution of scaffold forming proteins
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Bacterial cellulose-hydroxyapatite composites with osteogenic growth peptide (OGP) or pentapeptide OGP on bone regeneration in critical-size calvarial defect model
Pigossi, S. C., de Oliveira, G. J. P. L., Finoti, L. S., Nepomuceno, R., Spolidório, L. C., Rossa, C., Ribeiro, S. J. L., Saska, S., & Scarel‐Caminaga, R. M. (2015) · Journal of Biomedical Materials Research Part A · doi:10.1002/jbm.a.35472 · Cited by 63 · see citing works
In vitro and in vivo investigation on biodegradable Mg-Li-Ca alloys for bone implant application
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Engineering High-Resolution Micropatterns Directly onto Titanium with Optimized Contact Guidance to Promote Osteogenic Differentiation and Bone Regeneration
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Rutin promotes osteogenic differentiation of periodontal ligament stem cells through the GPR30-mediated PI3K/AKT/mTOR signaling pathway
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Synergistic effect of extracellularly supplemented osteopontin and osteocalcin on stem cell proliferation, osteogenic differentiation, and angiogenic properties
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Hydrolyzed tilapia fish collagen induces osteogenic differentiation of human periodontal ligament cells
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Relationship between Structure and Biological Activity of Various Vitamin K Forms
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Vitamin K2 Prevents Glucocorticoid-induced Osteonecrosis of the Femoral Head in Rats
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The Bone—Vasculature Axis: Calcium Supplementation and the Role of Vitamin K
Wasilewski, G. B., Vervloet, M. G., & Schurgers, L. J. (2019) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2019.00006 · Cited by 59 · see citing works
Effect of Aerobic Exercise on Markers of Bone Metabolism of Overweight and Obese Patients With Chronic Kidney Disease
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Bone turnover markers and novel biomarkers in lung cancer bone metastases
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N-acetyl cysteine inhibits H2O2-mediated reduction in the mineralization of MC3T3-E1 cells by down-regulating Nrf2/HO-1 pathway
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Icariin Protects against Glucocorticoid-Induced Osteonecrosis of the Femoral Head in Rats
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In Vitro Co-Culture Model of Primary Human Osteoblasts and Osteocytes in Collagen Gels
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Circadian disruption by shifting the light‐dark cycle negatively affects bone health in mice
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Cobalt chloride supplementation induces stem-cell marker expression and inhibits osteoblastic differentiation in human periodontal ligament cells
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A review of in vitro cell culture testing methods for bioactive glasses and other biomaterials for hard tissue regeneration
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Bone changes in alcoholic liver disease
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Locally controlled delivery of TNFα antibody from a novel glucose-sensitive scaffold enhances alveolar bone healing in diabetic conditions
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Albiflorin Promotes Osteoblast Differentiation and Healing of Rat Femoral Fractures Through Enhancing BMP-2/Smad and Wnt/β-Catenin Signaling
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Authors: Neve, A., Corrado, A., & Cantatore, F. P.
Affiliations: University of Foggia (IT)
Corresponding author: Cantatore, Francesco Paolo
ORCID: Corrado, Addolorata
Cantatore, Francesco Paolo
Venue: Journal of Cellular Physiology
Publisher: Wiley
Published: 2013-02-25
Volume: 228
Issue: 6
Pages: 1149-1153
ISSN: 0021-9541 (ISSN-L)
1097-4652
DOI: 10.1002/jcp.24278
OpenAlex: W2093489016
Cited by: 335
References: 100
Citations by year: 2026: 8 · 2025: 14 · 2024: 15 · 2023: 20 · 2022: 27 · 2021: 38 · 2020: 30 · 2019: 27 · 2018: 33 · 2017: 27 · 2016: 19 · 2015: 38 · 2014: 28 · 2013: 11
FWCI: 2.25
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations: Journal of Cellular Physiology (publishedVersion)
PubMed (publishedVersion)
Institutional Research Information System University of Ferrara (University of Ferrara) (submittedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
Health Sciences › Medicine › Rheumatology › Bone and Dental Protein Studies
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Alkaline Phosphatase Research Studies
Keywords: osteocalcin, vitamin K-dependent proteins, gamma-carboxyglutamic acid, bone mineralization, osteogenic differentiation, osteoclast activity, vitamin D3, uncarboxylated osteocalcin, beta-cell function, insulin secretion, adiponectin, glucose metabolism, energy metabolism, angiogenesis, vascular calcification
MeSH terms: Animals, Bone and Bones, Calcinosis, Energy Metabolism, Gene Expression Regulation, Humans, Osteoblasts, Osteocytes, Signal Transduction, Osteocalcin, Bone Remodeling, Neovascularization, Physiologic, Adiposity

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Osteocalcin: Skeletal and extra‐skeletal effects

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