Osteocalcin TechNotes

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Osteocalcin (OC), which is also known as bone Glaprotein (BGP), is a vitamin K-dependent bone matrix peptide of 49 amino acid residues. The concentration of OC in serum is considered to be an index of bone formation and numerous immunoassays for the measurement of OC have been developed in order to evaluate its potential role in reflecting metabolic disorders to bone.

Although most of the synthesized human OC (hOC) is bound to bone hydroxyapatite, a small part of it leaks into the bloodstream. hOC concentrations in the circulation have been used in clinical investigations as a marker of bone formation. However, the discordant results obtained with different hOC assays have hindered the widespread usage of hOC in clinical applications.

The protein contains three g-carboxyglutamic acids (Gla) that interact with Ca2/ ions on the surface of the hydroxyapatite, which is the major mineral componentof bone. Although OC is predominantly associated with bone, a fraction of the newly synthesized protein is released into circulation where the status of the bone metabolism can be measured. The concentration of hOC increases in a variety of conditions that are characterized by increased bone turnover, such as osteoporosis, puberty, primary and secondary hyperparathyroidism, hyperthyroidism, and Paget’s disease. Its concentration decreases correspondingly in hypothyroidism, hypoparathyroidism, as well as in patients receiving glucocorticoid treatment.

The structure of osteocalcin is also well conserved in many vertebrate species. Therefore, it is difficult to raise antibodies against it in animals even if chemically coupled to various carrier molecules. On account of this it might be reasonable to produce recombinant osteocalcin as a fusion protein and subsequently use it as an immunogen for the development of new osteocalcin assays based on monoclonal antibodies (MAbs). In addition, the utilization of recombinant osteocalcin for the standardization of osteocalcin assays is also an advantage. This is because the purification of hOC from bone is a laborious and timeconsuming procedure.

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