, Volume 48, Issue 2, pp 394–404 | Cite as

A four-season molecule: osteocalcin. Updates in its physiological roles

  • Giovanni Lombardi
  • Silvia Perego
  • Livio Luzi
  • Giuseppe Banfi


Osteocalcin (OC) is the main non-collagenous hydroxyapatite-binding protein synthesized by osteoblasts, odontoblasts, and hypertrophic chondrocytes. It has a regulatory role in mineralization and it is considered a marker of bone cell metabolism. Recent findings evidenced new extra-skeletal roles for OC, depicting it as a real hormone. OC shares many functional features with the common hormones, such as tissue-specific expression, circadian rhythm, and synthesis as a pre-pro-molecule. However, it has some peculiar features making it a unique molecule: OC exists in different forms based on the degree of carboxylation. Indeed, OC has three glutamic acid residues, in position 17, 21, and 24, which are subject to γ-carboxylation, through the action of a vitamin K-dependent γ-glutamyl carboxytransferase. The degree of carboxylation, and thus the negative charge density, determines the affinity for the calcium ions deposited in the extracellular matrix of the bone. The modulation of the carboxylation could, thus, represent the mechanism by which the body controls the circulating levels, and hence the hormonal function, of OC. There are evidences linking OC, and the bone metabolism, with a series of endocrine (glucose metabolism, energy metabolism, fertility) physiological (muscle activity) and pathological functions (ectopic calcification). Aim of this review is to give a full overview of the physiological roles of OC by collecting the newest experimental findings on this intriguing molecule.


γ-Glutamyl transferases Bone turnover Energy metabolism Fertility Muscle strength Ectopic calcification 



This work has been funded by the Italian Ministry of Health.


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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Giovanni Lombardi
    • 1
  • Silvia Perego
    • 1
  • Livio Luzi
    • 2
    • 3
  • Giuseppe Banfi
    • 1
    • 2
  1. 1.Laboratory of Experimental Biochemistry & Molecular BiologyI.R.C.C.S. Istituto Ortopedico GaleazziMilanItaly
  2. 2.Department of Biomedical Sciences for HealthUniversity of MilanoMilanItaly
  3. 3.Division of Endocrinology and Metabolic DiseasesI.R.C.C.S. Policlinico San DonatoSan Donato MilaneseItaly

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