Osteocalcin, also known as bone gamma-carboxyglutamic acid-containing protein (BGLAP), is a noncollagenous protein found in bone and dentin. Because it has gla domains, its synthesis is vitamin K dependent. In humans, the osteocalcin is encoded by the BGLAPgene. Its receptor is GPRC6A.
Osteocalcin is secreted solely by osteoblasts and thought to play a role in the body's metabolic regulation and is pro-osteoblastic, or bone-building, by nature. It is also implicated in bone mineralization and calcium ion homeostasis. Osteocalcin acts as a hormone in the body, causing beta cells in the pancreas to release more insulin, and at the same time directing fat cells to release the hormone adiponectin, which increases sensitivity to insulin.
Current data suggests a possible role of osteocalcin in male fertility. Research from Columbia University Medical Center proposes that osteocalcin may enhance the synthesis of testosterone. Although these studies were initially performed by only a single laboratory, at least two other groups have independently confirmed the role of osteocalcin in insulin secretion.
Use as a biochemical marker for bone formation
As osteocalcin is produced by osteoblasts, it is often used as a marker for the bone formation process. It has been observed that higher serum-osteocalcin levels are relatively well correlated with increases in bone mineral density (BMD) during treatment with anabolic bone formation drugs for osteoporosis, such as Teriparatide. In many studies, osteocalcin is used as a preliminary biomarker on the effectiveness of a given drug on bone formation. For instance, one study which aimed to study the effectiveness of a glycoprotein called lactoferrin on bone formation used osteocalcin as a measure of osteoblast activity.
^Puchacz E, Lian JB, Stein GS, Wozney J, Huebner K, Croce C (May 1989). "Chromosomal localization of the human osteocalcin gene". Endocrinology124 (5): 2648–50. doi:10.1210/endo-124-5-2648. PMID2785029.
^Cancela L, Hsieh CL, Francke U, Price PA (September 1990). "Molecular structure, chromosome assignment, and promoter organization of the human matrix Gla protein gene". J. Biol. Chem.265 (25): 15040–8. PMID2394711.
^Franck Oury, Grzegorz Sumara, Olga Sumara, Mathieu Ferron, Haixin Chang, Charles E. Smith, Louis Hermo, Susan Suarez, Bryan L. Roth, Patricia Ducy et al. Endocrine Regulation of Male Fertility by the Skeleton. Cell, 17 February 2011 doi:10.1016/j.cell.2011.02.004
Kamdem LK, Hamilton L, Cheng C, et al. (2008). "Genetic predictors of glucocorticoid-induced hypertension in children with acute lymphoblastic leukemia.". Pharmacogenet. Genomics18 (6): 507–14. doi:10.1097/FPC.0b013e3282fc5801. PMID18496130.
Lin GT, Tseng HF, Chang CK, et al. (2008). "SNP combinations in chromosome-wide genes are associated with bone mineral density in Taiwanese women.". Chin J Physiol51 (1): 32–41. PMID18551993.
Lumachi F, Camozzi V, Tombolan V, Luisetto G (2009). "Bone mineral density, osteocalcin, and bone-specific alkaline phosphatase in patients with insulin-dependent diabetes mellitus.". Annals of the New York Academy of Sciences. 1173 Suppl 1: E64–7. doi:10.1111/j.1749-6632.2009.04955.x. PMID19751417.
Kanazawa I, Yamaguchi T, Yamamoto M, et al. (2009). "Serum osteocalcin/bone-specific alkaline phosphatase ratio is a predictor for the presence of vertebral fractures in men with type 2 diabetes.". Calcif. Tissue Int.85 (3): 228–34. doi:10.1007/s00223-009-9272-4. PMID19641839.
Makita N, Suzuki M, Asami S, et al. (2008). "Two of four alternatively spliced isoforms of RUNX2 control osteocalcin gene expression in human osteoblast cells.". Gene413 (1-2): 8–17. doi:10.1016/j.gene.2007.12.025. PMID18321663.
Ba Y, Huang H, Yang Y, et al. (2009). "The association between osteocalcin gene polymorphism and dental fluorosis among children exposed to fluoride in People's Republic of China.". Ecotoxicol. Environ. Saf.72 (8): 2158–61. doi:10.1016/j.ecoenv.2009.08.014. PMID19767102.
Hwang YC, Jeong IK, Ahn KJ, Chung HY (2009). "The uncarboxylated form of osteocalcin is associated with improved glucose tolerance and enhanced beta-cell function in middle-aged male subjects.". Diabetes Metab. Res. Rev.25 (8): 768–72. doi:10.1002/dmrr.1045. PMID19877133.
Kindblom JM, Ohlsson C, Ljunggren O, et al. (2009). "Plasma osteocalcin is inversely related to fat mass and plasma glucose in elderly Swedish men.". J. Bone Miner. Res.24 (5): 785–91. doi:10.1359/jbmr.081234. PMID19063687.
Wahlgren CM, Zheng W, Shaalan W, et al. (2009). "Human carotid plaque calcification and vulnerability. Relationship between degree of plaque calcification, fibrous cap inflammatory gene expression and symptomatology.". Cerebrovasc. Dis.27 (2): 193–200. doi:10.1159/000189204. PMID19136823.
Lumachi F, Ermani M, Camozzi V, et al. (2009). "Changes of bone formation markers osteocalcin and bone-specific alkaline phosphatase in postmenopausal women with osteoporosis.". Annals of the New York Academy of Sciences. 1173 Suppl 1: E60–3. doi:10.1111/j.1749-6632.2009.04953.x. PMID19751416.
Born AK, Rottmar M, Lischer S, et al. (2009). "Correlating cell architecture with osteogenesis: first steps towards live single cell monitoring.". Eur Cell Mater18: 49–60, 61–2; discussion 60. PMID19856264.
Fujisawa R (2002). "[Recent advances in research on bone matrix proteins]". Nippon Rinsho. 60 Suppl 3: 72–8. PMID11979972.