Osteocalcin, also known asbone gamma-carboxyglutamic acid-containing protein (BGLAP), is a small (49-amino-acid[5]) noncollagenousproteinhormone found in bone anddentin, first identified as a calcium-binding protein.[6]
Because osteocalcin hasgla domains, its synthesis isvitamin K2-dependent. In humans, osteocalcin is encoded by theBGLAPgene.[7][8] Its receptors includeGPRC6A,GPR158, and possibly a third, yet-to-be-identified receptor.[9][10] There is evidence thatGPR37 might be the third osteocalcin receptor.[11]
Osteocalcin is secreted solely byosteoblasts and is thought to play a role in the body's metabolic regulation.[12] In itscarboxylated form, calcium is bound directly to the bone and thus concentrates here.
In its uncarboxylated form, osteocalcin acts as ahormone in the body, signalling in the pancreas, fat, muscle, testes, and brain.[13]
In the brain, osteocalcin plays an important role in development and functioning, including spatial learning and memory.[17]
Anacute stress response (ASR), colloquially known as the fight-or-flight response, stimulates osteocalcin release from bone within minutes in mice, rats, and humans. Injections of high levels of osteocalcin alone can trigger an ASR in the presence ofadrenal insufficiency.[18]
As osteoblasts produce osteocalcin, it is often used as a marker for thebone formation process. Higher serum osteocalcin levels have been observed to correlate relatively well with increases inbone mineral density during treatment with anabolic bone formation drugs forosteoporosis, such asteriparatide. In many studies, osteocalcin is used as a preliminarybiomarker for the effectiveness of a given drug on bone formation. For instance, one study that aimed to study the efficacy of aglycoprotein calledlactoferrin on bone formation used osteocalcin to measure osteoblast activity.[19]
^"Human PubMed Reference:".National Center for Biotechnology Information, U.S. National Library of Medicine.
^"Mouse PubMed Reference:".National Center for Biotechnology Information, U.S. National Library of Medicine.
^Hauschka PV, Carr SA, Biemann K (February 1982). "Primary structure of monkey osteocalcin".Biochemistry.21 (4):638–642.doi:10.1021/bi00533a006.PMID6978733.
^Hauschka PV, Reid ML (August 1978). "Timed appearance of a calcium-binding protein containing gamma-carboxyglutamic acid in developing chick bone".Developmental Biology.65 (2):426–434.doi:10.1016/0012-1606(78)90038-6.PMID680371.
^Puchacz E, Lian JB, Stein GS, Wozney J, Huebner K, Croce C (May 1989). "Chromosomal localization of the human osteocalcin gene".Endocrinology.124 (5):2648–50.doi:10.1210/endo-124-5-2648.PMID2785029.
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Lin GT, Tseng HF, Chang CK, Chuang LY, Liu CS, Yang CH, et al. (February 2008). "SNP combinations in chromosome-wide genes are associated with bone mineral density in Taiwanese women".The Chinese Journal of Physiology.51 (1):32–41.PMID18551993.
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Kanazawa I, Yamaguchi T, Yamamoto M, Yamauchi M, Yano S, Sugimoto T (September 2009). "Serum osteocalcin/bone-specific alkaline phosphatase ratio is a predictor for the presence of vertebral fractures in men with type 2 diabetes".Calcified Tissue International.85 (3):228–34.doi:10.1007/s00223-009-9272-4.PMID19641839.S2CID21508194.
Makita N, Suzuki M, Asami S, Takahata R, Kohzaki D, Kobayashi S, et al. (April 2008). "Two of four alternatively spliced isoforms of RUNX2 control osteocalcin gene expression in human osteoblast cells".Gene.413 (1–2):8–17.doi:10.1016/j.gene.2007.12.025.PMID18321663.
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Salem AM, Zohny SF, Abd El-Wahab MM, Hamdy R (November 2007). "Predictive value of osteocalcin and beta-CrossLaps in metastatic breast cancer".Clinical Biochemistry.40 (16–17):1201–8.doi:10.1016/j.clinbiochem.2007.07.006.PMID17889845.
Im JA, Yu BP, Jeon JY, Kim SH (October 2008). "Relationship between osteocalcin and glucose metabolism in postmenopausal women".Clinica Chimica Acta; International Journal of Clinical Chemistry.396 (1–2):66–9.doi:10.1016/j.cca.2008.07.001.PMID18657532.
Ba Y, Huang H, Yang Y, Cui L, Zhu J, Zhu C, et al. (November 2009). "The association between osteocalcin gene polymorphism and dental fluorosis among children exposed to fluoride in People's Republic of China".Ecotoxicology and Environmental Safety.72 (8):2158–61.Bibcode:2009EcoES..72.2158B.doi:10.1016/j.ecoenv.2009.08.014.PMID19767102.
Hwang YC, Jeong IK, Ahn KJ, Chung HY (November 2009). "The uncarboxylated form of osteocalcin is associated with improved glucose tolerance and enhanced beta-cell function in middle-aged male subjects".Diabetes/Metabolism Research and Reviews.25 (8):768–72.doi:10.1002/dmrr.1045.PMID19877133.S2CID39181400.
Kindblom JM, Ohlsson C, Ljunggren O, Karlsson MK, Tivesten A, Smith U, et al. (May 2009). "Plasma osteocalcin is inversely related to fat mass and plasma glucose in elderly Swedish men".Journal of Bone and Mineral Research.24 (5):785–91.doi:10.1359/jbmr.081234.PMID19063687.S2CID207269385.
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