Osteocalcin, also known as bone gamma-carboxyglutamic acid-containing protein (BGLAP), is a small (49-amino-acid) noncollagenous proteinhormone found in bone and dentin, first identified as a calcium-binding protein in chick bone.
Because osteocalcin has gla domains, its synthesis is vitamin K dependent. In humans, osteocalcin is encoded by the BGLAPgene. Its receptors include GPRC6A, GPR158, and possibly a third, yet-to-be-identified receptor. There is evidence that GPR37 might be the third osteocalcin receptor.
In the brain, osteocalcin plays an important role in development and functioning.
An acute 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 of adrenal insufficiency.
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 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.
^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): 426–34. 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.
^Bharadwaj S, Naidu AG, Betageri GV, Prasadarao NV, Naidu AS (September 2009). "Milk ribonuclease-enriched lactoferrin induces positive effects on bone turnover markers in postmenopausal women". Osteoporosis International. 20 (9): 1603–11. doi:10.1007/s00198-009-0839-8. PMID19172341. S2CID10711802.
Kamdem LK, Hamilton L, Cheng C, Liu W, Yang W, Johnson JA, et al. (June 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. S2CID1251203.
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.
Lumachi F, Camozzi V, Tombolan V, Luisetto G (September 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. S2CID9796894.
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.
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. 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, 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. S2CID207269385.
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. S2CID34370256.
Lumachi F, Ermani M, Camozzi V, Tombolan V, Luisetto G (September 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. S2CID1149818.
Born AK, Rottmar M, Lischer S, Pleskova M, Bruinink A, Maniura-Weber K (October 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 (March 2002). "[Recent advances in research on bone matrix proteins]". Nihon Rinsho. Japanese Journal of Clinical Medicine. 60 Suppl 3: 72–8. PMID11979972.