Osteocalcin

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Osteocalcin
Properties of human protein
Mass / length primary structure 49 amino acids
Precursor (100 aa)
Identifier
Gene name BGLAP
External IDs
Occurrence
Parent taxon Euteleostomi

Osteocalcin (synonym: “ b one γ- carboxylglutamic acid-containing p rotein” or: “BGP” , the gene: BGLAP ) is a peptide hormone discovered in 1975 in the body of most vertebrates . It is formed in the bone by the osteoblasts and in the tooth by the odontoblasts and binds to hydroxyapatite and calcium . It is part (one to two percent) of the extracellular non-collagenous bone matrix . Osteocalcin is a marker of bone structure and inhibits the mineralization of the bone. Osteocalcin could be extracted from the bones of the Neanderthal man in a completely preserved form . In mice, even the smallest amounts of osteocalcin stimulate the release of insulin and the breakdown of fat cells .

Layout and function

Human osteocalcin consists of 49 amino acids . Osteocalcin is encoded in humans by a gene on chromosome 1q25-q31. Its synthesis is induced in osteoblasts of 1.25 (OH) VitD 3 . In the experiment in mice, the deactivation of the gene leads to an abnormally increased bone mineralization and increase in bone substance with simultaneously reduced breaking strength and narrowing of the marrow cavity, a characteristic of osteopetrosis (marble bone disease).

Osteocalcin contains glutamyl residues , which have to be γ-carboxylated with the help of the cofactor vitamin K and the enzyme Γ-glutamylcarboxylase before osteocalcin can actively bind calcium in the bone. The bone matrix contains approx. 2% osteocalcin. Osteocalcin has calcium-binding properties in common with other calcium- binding proteins (e.g. calbindin or specific coagulation factors ).

The latest research findings, which have yet to be confirmed for humans, assign osteocalcin a function that lowers blood sugar and promotes fat breakdown. Osteocalcin apparently acts on the sugar metabolism a) directly: by stimulating insulin production in the β-cells of the islets of Langerhans in the pancreas; and possibly b) indirectly: by promoting the release of adiponectin , which increases the effectiveness of insulin . Osteocalcin apparently causes an increased breakdown of fat in the body fat deposits. In animal experiments, mice with high osteocalcin levels in the serum proved to be resistant to diabetes and obesity, on the other hand, mice with a lack of osteocalcin in the serum suffered from diabetes and obesity. The newly discovered metabolic functions of osteocalcin may require new approaches to diabetes II therapy.

In February 2011, a US research group published the results of research that indicated that osteocalcin promotes fertility in male mice. By binding to a G-protein-coupled receptor in the Leydig cells of the testis, it regulates the expression of enzymes that are necessary for testosterone production in a CREB- dependent manner . As a result, osteocalcin causes the survival of male germ cells . On the other hand, it does not seem to have any effect on estrogen production in female animals. This was the first time that a regulatory influence of the skeleton on fertility was demonstrated.

Osteocalcin affects the production of neurotransmitters such as serotonin, dopamine and others in the brain. It supports learning and spatial memory. In laboratory tests, osteocalcin appears to improve age-related deterioration in performance in memory tasks and the recognition of new objects in mice.

Laboratory values

Osteocalcin is a marker of bone formation with good diagnostic specificity . Osteocalcin can be detected in the blood and urine . The method used for this purpose provision is a chemiluminescence - immunoassay . The osteocalcin is determined to assess bone turnover in osteoporosis or plasmacytoma . The osteocalcin level can also be used to check the effectiveness of calcitriol therapy. Osteocalcin has a plasma half-life of 4 minutes. It is excreted through the kidneys. With a reduced kidney function, increased osteocalcin values ​​can only be utilized to a limited extent. Hereditary factors (variants of the vitamin D receptor ) can also be responsible for changed values in individual people .

increased values
lowered values

The normal range for children and adolescents between 2 and 17 years of age is 2.8 to 41 µg / l , with a sharp increase during the pubertal growth spurt . In adults, the normal range is 3 to 14 µg / l.

literature

  • G. Muyzer, P. Sandberg, MHJ Knapen, C. Vermeer, MJ Collins, P. Westbroek: Preservation of bone protein osteocalcin in dinosaurs. In: Geology. Volume 20, 1992, pp. 871-874.
  • CM Gundberg, PV Hauschka, JB Lian, PM Gallop: Osteocalcin: isolation, characterization, and detection. In: Methods Enzymol. 107, 1984, pp. 516-444.
  • LJ Schedlich, JL Flanagan, LA Crofts, SA Gillies, D. Goldberg, NA Morrison, JA Eisman: Transcriptional activation of the human osteocalcin gene by basic fibroblast growth factor. In: J Bone Miner Res. 9 (2), Feb 1994, pp. 143-152.
  • C. Nielsen-Marsh, PH Ostrom, H. Gandhi, B. Shapiro, A. Cooper, PV Hauschka, MJ Collins: Sequence preservation of osteocalcin protein and mitochondrial DNA in bison bones older than 55ka. In: Geology. 30, 2002, pp. 1099-1102.
  • C. Nielsen-Marsh: Biomolecules in fossil remains. In: The Biochemist. Volume 24, No. 3, June 2002, pp. 12-14.
  • Christina M. Nielsen-Marsh, Michael P. Richards, Peter V. Hauschka, Jane E. Thomas-Oates, Erik Trinkaus , Paul B. Pettitt , Ivor Karavanic, Hendrik Poinar, Matthew J. Collins: Osteocalcin protein sequences of Neanderthals and modern primates. In: PNAS . published March 7, 2005, doi: 10.1073 / pnas.0500450102 .

See also

Web links

Individual evidence

  1. ↑ The study comes from a research group headed by Gerard Karsenty, Na Kyung Lee and colleagues, most of whom belong to the Department of Genetics & Development (College of Physicians and Surgeons) at Columbia University in New York, NY 10032, USA, and was published in: Cell. Volume 130, Aug 10, 2007, pp. 456-469. ( cumc.columbia.edu ( Memento from October 7, 2008 in the Internet Archive ))
  2. ↑ M. Ferron et al .: Osteocalcin differentially regulates beta cell and adipocyte gene expression and affects the development of metabolic diseases in wild-type mice. In: Proc. Nat. Acad. Sci. 105, 2008, pp. 5266-5270. PMID 18362359
  3. ^ Franck Oury et al: Endocrine Regulation of Male Fertility by the Skeleton. In: Cell. Volume 144, No. 5, March 2011, pp. 796-809. doi: 10.1016 / j.cell.2011.02.004 .
  4. ↑ Franck Oury et al.:Maternal and Offspring Pools of osteocalcin Influence Brain Development and Function. Cell 155, 1 (2013), pp. 228-241.
  5. ↑ Eric Kandel, The Disordered Mind. Farrar, Staus Giroux, New York (2018).