Osteocalcin and matrix Gla protein: vitamin K-dependent proteins in bone

How pleiotropic genetics of the musculoskeletal system can inform genomics and phenomics of aging

“…Osteocalcin Osteo calcin (OC, or gammacarboxyglutamic acid protein) comprises about 15% of the non-collagenous protein component of the extracellular bone matrix and is the most abundant non-collagenous protein of the human body (Hauschka et al 1989). The majority of osteocalcin is synthesized by osteoblasts and becomes incorporated into the bone matrix by binding to hydroxyapatite (Hauschka 1986); as such, OC serum concentrations reflect osteoblastic activity and the rate of bone formation.…”

Structural Evidence of a Fourth Gla Residue in Fish Osteocalcin: Biological Implications,

“…This small protein of 46-50 amino acid residues (depending on the species) (4, 5) is secreted mainly by osteoblasts. It is also one of the most abundant (10-20%) noncollagenous proteins in bones of most vertebrates examined to date, from bony fish to mammals (depending on species, age, and site) (4,(6)(7)(8)(9).Conserved elements in all osteocalcin sequences examined to date include a single disulfide bond (Cys 17 -Cys 23 ) using Argyrosomus regius amino acid sequence numbering, and three γ-carboxyglutamic acid residues (Gla) located at positions 11, 15, and 18 (4, 9-13). These Gla residues are thought to facilitate adsorption of osteocalcin to hydroxyapatite (10,14,15) and are located in the central, conserved portion of the molecule.…”

“…These Gla residues are thought to facilitate adsorption of osteocalcin to hydroxyapatite (10,14,15) and are located in the central, conserved portion of the molecule. In contrast, its N-terminal part exhibits considerable sequence variation (4,8,9,13).Initial studies showed that osteocalcin binds strongly to hydroxyapatite crystals (7) and affects mineral formation and mineral crystal growth in solution (16,17). Several studies also suggested a role for osteocalcin as a matrix signal for the recruitment and differentiation of osteoclasts (18-21).…”

Characterization of Osteocalcin (BGP) and Matrix Gla Protein (MGP) Fish Specific Antibodies: Validation for Immunodetection Studies in Lower Vertebrates

“…Each antibody recognized either BGP or MGP with no cross-reaction between proteins detected. All purified fish BGPs and MGPs tested were shown to be specifically recognized, thus validating the use of these antibodies for further studies.Matrix Gla Protein (MGP) and Bone Gla Protein (BGP, osteocalcin) belong to the family of vitamin K-dependent (VKD), c-carboxyglutamic acid (Gla)-containing proteins that have been unequivocally associated with bone formation and mineralization [1][2][3][4], and more recently, with vascular calcification [5][6][7][8][9][10].MGP is a 10-15 kDa-secreted protein, containing 4-5 residues (depending on the species) of the Ca 2+ binding Gla residue [11][12][13][14][15] while BGP is a small secreted protein with approximately 6 kDa molecular weight and includes three Gla residues. Although there is little information about the regulation of expression of these proteins in teleosts, BGP in teleost fish has been shown to be associated with bone-like mineralized tissues present in branchial arches, jaw, vertebra and scales [15,16] while MGP was only recently found to accumulate, mainly in the extracellular matrix of calcified cartilage [15].…”

“…Matrix Gla Protein (MGP) and Bone Gla Protein (BGP, osteocalcin) belong to the family of vitamin K-dependent (VKD), c-carboxyglutamic acid (Gla)-containing proteins that have been unequivocally associated with bone formation and mineralization [1][2][3][4], and more recently, with vascular calcification [5][6][7][8][9][10].…”