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.
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". Endocrinology. 124 (5): 2648–50. doi:10.1210/endo-124-5-2648. PMID2785029.
^Cancela L, Hsieh CL, Francke U, Price PA (Sep 1990). "Molecular structure, chromosome assignment, and promoter organization of the human matrix Gla protein gene". The Journal of Biological Chemistry. 265 (25): 15040–8. PMID2394711.
^Pi M, Wu Y, Quarles LD (Jul 2011). "GPRC6A mediates responses to osteocalcin in β-cells in vitro and pancreas in vivo". Journal of Bone and Mineral Research. 26 (7): 1680–1683. doi:10.1002/jbmr.390. PMID21425331.
Kamdem LK, Hamilton L, Cheng C, Liu W, Yang W, Johnson JA, Pui CH, Relling MV (Jun 2008). "Genetic predictors of glucocorticoid-induced hypertension in children with acute lymphoblastic leukemia". Pharmacogenetics and Genomics. 18 (6): 507–14. doi:10.1097/FPC.0b013e3282fc5801. PMID18496130.
Lin GT, Tseng HF, Chang CK, Chuang LY, Liu CS, Yang CH, Tu CJ, Wang EC, Tan HF, Chang CC, Wen CH, Chen HC, Chang HW (Feb 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.
Lumachi F, Camozzi V, Tombolan V, Luisetto G (Sep 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, Yamauchi M, Yano S, Sugimoto T (Sep 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.
Makita N, Suzuki M, Asami S, Takahata R, Kohzaki D, Kobayashi S, Hakamazuka T, Hozumi N (Apr 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.
Desbois C, Karsenty G (Mar 1995). "Osteocalcin cluster: implications for functional studies". Journal of Cellular Biochemistry. 57 (3): 379–83. doi:10.1002/jcb.240570302. PMID7768973.
Im JA, Yu BP, Jeon JY, Kim SH (Oct 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, Liu J, Zhang Y (Nov 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. doi:10.1016/j.ecoenv.2009.08.014. PMID19767102.
Hwang YC, Jeong IK, Ahn KJ, Chung HY (Nov 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.
Kindblom JM, Ohlsson C, Ljunggren O, Karlsson MK, Tivesten A, Smith U, Mellström D (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.
Wahlgren CM, Zheng W, Shaalan W, Tang J, Bassiouny HS (2009). "Human carotid plaque calcification and vulnerability. Relationship between degree of plaque calcification, fibrous cap inflammatory gene expression and symptomatology". Cerebrovascular Diseases. 27 (2): 193–200. doi:10.1159/000189204. PMID19136823.
Lumachi F, Ermani M, Camozzi V, Tombolan V, Luisetto G (Sep 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, Pleskova M, Bruinink A, Maniura-Weber K (2009). "Correlating cell architecture with osteogenesis: first steps towards live single cell monitoring". European Cells & Materials. 18: 49–60, 61–2; discussion 60. PMID19856264.
Fujisawa R (Mar 2002). "[Recent advances in research on bone matrix proteins]". Nihon Rinsho. Japanese Journal of Clinical Medicine. 60 Suppl 3: 72–8. PMID11979972.