Skip to main content
Top
Published in: Calcified Tissue International 1/2015

01-01-2015 | Review

Osteocalcin: An Osteoblast-Derived Polypeptide Hormone that Modulates Whole Body Energy Metabolism

Authors: Tara C. Brennan-Speranza, Arthur D. Conigrave

Published in: Calcified Tissue International | Issue 1/2015

Login to get access

Abstract

Osteocalcin is a bone-specific protein that is regularly used in the clinical setting as a serum marker of bone turnover. Recent evidence indicates that osteocalcin plays a previously unsuspected role in the control of energy metabolism. Thus, osteocalcin-deficient mice have a profoundly deranged metabolic phenotype that includes insulin resistance, glucose intolerance and abnormal fat deposition. Additionally, osteocalcin administration in mice improves insulin sensitivity and decreases fat pad mass and serum triglyceride levels. The role of osteocalcin in human macronutrient metabolism is less clear but recent studies report positive correlations between serum osteocalcin levels and established indices of metabolic health. Herein, we review key physiological functions of osteocalcin, focussing on the roles of osteocalcin in the modulation of macronutrient metabolism, male reproductive function and foetal brain development. We consider the implications of these findings for the coordination of metabolism with development and fertility. We also consider evidence that a Class C G-protein-coupled receptor from a subgroup known to mediate nutrient-sensing acts as the osteocalcin receptor.
Appendix
Available only for authorised users
Literature
1.
go back to reference Karsenty G (1998) Transcriptional regulation of osteoblast differentiation during development. Front Biosci 3:834–837 Karsenty G (1998) Transcriptional regulation of osteoblast differentiation during development. Front Biosci 3:834–837
2.
go back to reference Hauschka PV, Lian JB, Gallop PM (1975) Direct identification of the calcium-binding amino acid, gamma-carboxyglutamate, in mineralized tissue. Proc Natl Acad Sci USA 72:3925–3929CrossRefPubMedCentralPubMed Hauschka PV, Lian JB, Gallop PM (1975) Direct identification of the calcium-binding amino acid, gamma-carboxyglutamate, in mineralized tissue. Proc Natl Acad Sci USA 72:3925–3929CrossRefPubMedCentralPubMed
3.
go back to reference Price PA, Otsuka AA, Poser JW, Kristaponis J, Raman N (1976) Characterization of a gamma-carboxyglutamic acid-containing protein from bone. Proc Natl Acad Sci USA 73:1447–1451CrossRefPubMedCentralPubMed Price PA, Otsuka AA, Poser JW, Kristaponis J, Raman N (1976) Characterization of a gamma-carboxyglutamic acid-containing protein from bone. Proc Natl Acad Sci USA 73:1447–1451CrossRefPubMedCentralPubMed
4.
go back to reference Hauschka PV, Lian JB, Cole DE, Gundberg CM (1989) Osteocalcin and matrix Gla protein: vitamin K-dependent proteins in bone. Physiol Rev 69:990–1047PubMed Hauschka PV, Lian JB, Cole DE, Gundberg CM (1989) Osteocalcin and matrix Gla protein: vitamin K-dependent proteins in bone. Physiol Rev 69:990–1047PubMed
5.
go back to reference Karsenty G, Kronenberg HM, Settembre C (2009) Genetic control of bone formation. Annu Rev Cell Dev Biol 25:629–648CrossRefPubMed Karsenty G, Kronenberg HM, Settembre C (2009) Genetic control of bone formation. Annu Rev Cell Dev Biol 25:629–648CrossRefPubMed
6.
go back to reference Ducy P, Desbois C, Boyce B, Pinero G, Story B, Dunstan C, Smith E, Bonadio J, Goldstein S, Gundberg C, Bradley A, Karsenty G (1996) Increased bone formation in osteocalcin-deficient mice. Nature 382:448–452CrossRefPubMed Ducy P, Desbois C, Boyce B, Pinero G, Story B, Dunstan C, Smith E, Bonadio J, Goldstein S, Gundberg C, Bradley A, Karsenty G (1996) Increased bone formation in osteocalcin-deficient mice. Nature 382:448–452CrossRefPubMed
7.
go back to reference Murshed M, Schinke T, McKee MD, Karsenty G (2004) Extracellular matrix mineralization is regulated locally; different roles of two gla-containing proteins. J Cell Biol 165:625–630CrossRefPubMedCentralPubMed Murshed M, Schinke T, McKee MD, Karsenty G (2004) Extracellular matrix mineralization is regulated locally; different roles of two gla-containing proteins. J Cell Biol 165:625–630CrossRefPubMedCentralPubMed
8.
go back to reference Dubois-Ferrière V, Brennan TC, Dayer R, Rizzoli R, Ammann P (2011) Calcitropic hormones and IGF-I are influenced by dietary protein. Endocrinology 152:1839–1847CrossRefPubMed Dubois-Ferrière V, Brennan TC, Dayer R, Rizzoli R, Ammann P (2011) Calcitropic hormones and IGF-I are influenced by dietary protein. Endocrinology 152:1839–1847CrossRefPubMed
9.
go back to reference Rutter MM, Markoff E, Clayton L, Akeno N, Zhao G, Clemens TL, Chernausek SD (2005) Osteoblast-specific expression of insulin-like growth factor-1 in bone of transgenic mice induces insulin-like growth factor binding protein-5. Bone 36:224–231CrossRefPubMed Rutter MM, Markoff E, Clayton L, Akeno N, Zhao G, Clemens TL, Chernausek SD (2005) Osteoblast-specific expression of insulin-like growth factor-1 in bone of transgenic mice induces insulin-like growth factor binding protein-5. Bone 36:224–231CrossRefPubMed
10.
go back to reference Ferron M, McKee MD, Levine RL, Ducy P, Karsenty G (2012) Intermittent injections of osteocalcin improve glucose metabolism and prevent type 2 diabetes in mice. Bone 50:568–575CrossRefPubMedCentralPubMed Ferron M, McKee MD, Levine RL, Ducy P, Karsenty G (2012) Intermittent injections of osteocalcin improve glucose metabolism and prevent type 2 diabetes in mice. Bone 50:568–575CrossRefPubMedCentralPubMed
11.
go back to reference Lee NK, Sowa H, Hinoi E, Ferron M, Ahn JD, Confavreux C, Dacquin R, Mee PJ, McKee MD, Jung DY, Zhang Z, Kim JK, Mauvais-Jarvis F, Ducy P, Karsenty G (2007) Endocrine regulation of energy metabolism by the skeleton. Cell 130:456–469CrossRefPubMedCentralPubMed Lee NK, Sowa H, Hinoi E, Ferron M, Ahn JD, Confavreux C, Dacquin R, Mee PJ, McKee MD, Jung DY, Zhang Z, Kim JK, Mauvais-Jarvis F, Ducy P, Karsenty G (2007) Endocrine regulation of energy metabolism by the skeleton. Cell 130:456–469CrossRefPubMedCentralPubMed
12.
go back to reference Ferron M, Hinoi E, Karsenty G, Ducy P (2008) Osteocalcin differentially regulates β cell and adipocyte gene expression and affects the development of metabolic diseases in wild-type mice. Proc Natl Acad Sci 105:5266–5270CrossRefPubMedCentralPubMed Ferron M, Hinoi E, Karsenty G, Ducy P (2008) Osteocalcin differentially regulates β cell and adipocyte gene expression and affects the development of metabolic diseases in wild-type mice. Proc Natl Acad Sci 105:5266–5270CrossRefPubMedCentralPubMed
13.
go back to reference Eastell R, Delmas PD, Hodgson SF, Eriksen EF, Mann KG, Riggs BL (1988) Bone formation rate in older normal women: concurrent assessment with bone histomorphometry, calcium kinetics, and biochemical markers. J Clin Endocrinol Metab 67:741–748CrossRefPubMed Eastell R, Delmas PD, Hodgson SF, Eriksen EF, Mann KG, Riggs BL (1988) Bone formation rate in older normal women: concurrent assessment with bone histomorphometry, calcium kinetics, and biochemical markers. J Clin Endocrinol Metab 67:741–748CrossRefPubMed
14.
go back to reference Brown JP, Delmas PD, Malaval L, Edouard C, Chapuy MC, Meunier PJ (1984) Serum bone Gla-protein: a specific marker for bone formation in postmenopausal osteoporosis. Lancet 1:1091–1093CrossRefPubMed Brown JP, Delmas PD, Malaval L, Edouard C, Chapuy MC, Meunier PJ (1984) Serum bone Gla-protein: a specific marker for bone formation in postmenopausal osteoporosis. Lancet 1:1091–1093CrossRefPubMed
15.
go back to reference Seibel MJ (2006) Biochemical markers of bone turnover part II: clinical applications in the management of osteoporosis. Clin Biochem Rev 27:123–138PubMedCentralPubMed Seibel MJ (2006) Biochemical markers of bone turnover part II: clinical applications in the management of osteoporosis. Clin Biochem Rev 27:123–138PubMedCentralPubMed
16.
go back to reference Lian J, Stewart C, Puchacz E, Mackowiak S, Shalhoub V, Collart D, Zambetti G, Stein G (1989) Structure of the rat osteocalcin gene and regulation of vitamin D-dependent expression. Proc Natl Acad Sci USA 86:1143–1147CrossRefPubMedCentralPubMed Lian J, Stewart C, Puchacz E, Mackowiak S, Shalhoub V, Collart D, Zambetti G, Stein G (1989) Structure of the rat osteocalcin gene and regulation of vitamin D-dependent expression. Proc Natl Acad Sci USA 86:1143–1147CrossRefPubMedCentralPubMed
17.
go back to reference Boskey AL, Gadaleta S, Gundberg C, Doty SB, Ducy P, Karsenty G (1998) Fourier transform infrared microspectroscopic analysis of bones of osteocalcin-deficient mice provides insight into the function of osteocalcin. Bone 23:187–196CrossRefPubMed Boskey AL, Gadaleta S, Gundberg C, Doty SB, Ducy P, Karsenty G (1998) Fourier transform infrared microspectroscopic analysis of bones of osteocalcin-deficient mice provides insight into the function of osteocalcin. Bone 23:187–196CrossRefPubMed
18.
go back to reference Ducy P, Amling M, Takeda S, Priemel M, Schilling AF, Beil FT, Shen J, Vinson C, Rueger JM, Karsenty G (2000) Leptin inhibits bone formation through a hypothalamic relay: a central control of bone mass. Cell 100:197–207CrossRefPubMed Ducy P, Amling M, Takeda S, Priemel M, Schilling AF, Beil FT, Shen J, Vinson C, Rueger JM, Karsenty G (2000) Leptin inhibits bone formation through a hypothalamic relay: a central control of bone mass. Cell 100:197–207CrossRefPubMed
19.
go back to reference Takeda S, Elefteriou F, Levasseur R, Liu X, Zhao L, Parker KL, Armstrong D, Ducy P, Karsenty G (2002) Leptin regulates bone formation via the sympathetic nervous system. Cell 111:305–317CrossRefPubMed Takeda S, Elefteriou F, Levasseur R, Liu X, Zhao L, Parker KL, Armstrong D, Ducy P, Karsenty G (2002) Leptin regulates bone formation via the sympathetic nervous system. Cell 111:305–317CrossRefPubMed
20.
go back to reference Yadav VK, Oury F, Suda N, Liu ZW, Gao XB, Confavreux C, Klemenhagen KC, Tanaka KF, Gingrich JA, Guo XE, Tecott LH, Mann JJ, Hen R, Horvath TL, Karsenty G (2009) A serotonin-dependent mechanism explains the leptin regulation of bone mass, appetite, and energy expenditure. Cell 138:976–989CrossRefPubMedCentralPubMed Yadav VK, Oury F, Suda N, Liu ZW, Gao XB, Confavreux C, Klemenhagen KC, Tanaka KF, Gingrich JA, Guo XE, Tecott LH, Mann JJ, Hen R, Horvath TL, Karsenty G (2009) A serotonin-dependent mechanism explains the leptin regulation of bone mass, appetite, and energy expenditure. Cell 138:976–989CrossRefPubMedCentralPubMed
21.
go back to reference Mauro LJ, Olmsted EA, Skrobacz BM, Mourey RJ, Davis AR, Dixon JE (1994) Identification of a hormonally regulated protein tyrosine phosphatase associated with bone and testicular differentiation. J Biol Chem 269:30659–30667PubMed Mauro LJ, Olmsted EA, Skrobacz BM, Mourey RJ, Davis AR, Dixon JE (1994) Identification of a hormonally regulated protein tyrosine phosphatase associated with bone and testicular differentiation. J Biol Chem 269:30659–30667PubMed
22.
go back to reference Brennan-Speranza TC, Henneicke H, Gasparini SJ, Blankenstein KI, Heinevetter U, Cogger VC, Svistounov D, Zhang Y, Cooney GJ, Buttgereit F, Dunstan CR, Gundberg C, Zhou H, Seibel MJ (2012) Osteoblasts mediate the adverse effects of glucocorticoids on fuel metabolism. J Clin Invest 122:4172–4189CrossRefPubMedCentralPubMed Brennan-Speranza TC, Henneicke H, Gasparini SJ, Blankenstein KI, Heinevetter U, Cogger VC, Svistounov D, Zhang Y, Cooney GJ, Buttgereit F, Dunstan CR, Gundberg C, Zhou H, Seibel MJ (2012) Osteoblasts mediate the adverse effects of glucocorticoids on fuel metabolism. J Clin Invest 122:4172–4189CrossRefPubMedCentralPubMed
23.
go back to reference Buitenhuis HC, Soute BAM, Vermeer C (1990) Comparison of the vitamins K1, K2 and K3 as cofactors for the hepatic vitamin K-dependent carboxylase. Biochim Biophys Acta 1034:170–175CrossRefPubMed Buitenhuis HC, Soute BAM, Vermeer C (1990) Comparison of the vitamins K1, K2 and K3 as cofactors for the hepatic vitamin K-dependent carboxylase. Biochim Biophys Acta 1034:170–175CrossRefPubMed
24.
go back to reference Hotta K, Funahashi T, Bodkin NL, Ortmeyer HK, Arita Y, Hansen BC, Matsuzawa Y (2001) Circulating concentrations of the adipocyte protein adiponectin are decreased in parallel with reduced insulin sensitivity during the progression to type 2 diabetes in rhesus monkeys. Diabetes 50:1126–1133CrossRefPubMed Hotta K, Funahashi T, Bodkin NL, Ortmeyer HK, Arita Y, Hansen BC, Matsuzawa Y (2001) Circulating concentrations of the adipocyte protein adiponectin are decreased in parallel with reduced insulin sensitivity during the progression to type 2 diabetes in rhesus monkeys. Diabetes 50:1126–1133CrossRefPubMed
25.
go back to reference Yamauchi T, Kamon J, Waki H, Terauchi Y, Kubota N, Hara K, Mori Y, Ide T, Murakami K, Tsuboyama-Kasaoka N, Ezaki O, Akanuma Y, Gavrilova O, Vinson C, Reitman ML, Kagechika H, Shudo K, Yoda M, Nakano Y, Tobe K, Nagai R, Kimura S, Tomita M, Froguel P, Kadowaki T (2001) The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity. Nat Med 7:941–946CrossRefPubMed Yamauchi T, Kamon J, Waki H, Terauchi Y, Kubota N, Hara K, Mori Y, Ide T, Murakami K, Tsuboyama-Kasaoka N, Ezaki O, Akanuma Y, Gavrilova O, Vinson C, Reitman ML, Kagechika H, Shudo K, Yoda M, Nakano Y, Tobe K, Nagai R, Kimura S, Tomita M, Froguel P, Kadowaki T (2001) The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity. Nat Med 7:941–946CrossRefPubMed
26.
go back to reference Berg AH, Combs TP, Du X, Brownlee M, Scherer PE (2001) The adipocyte-secreted protein Acrp30 enhances hepatic insulin action. Nat Med 7:947–953CrossRefPubMed Berg AH, Combs TP, Du X, Brownlee M, Scherer PE (2001) The adipocyte-secreted protein Acrp30 enhances hepatic insulin action. Nat Med 7:947–953CrossRefPubMed
27.
go back to reference Fruebis J, Tsao TS, Javorschi S, Ebbets-Reed D, Erickson MR, Yen FT, Bihain BE, Lodish HF (2001) Proteolytic cleavage product of 30-kDa adipocyte complement-related protein increases fatty acid oxidation in muscle and causes weight loss in mice. Proc Natl Acad Sci U S A 98:2005–2010CrossRefPubMedCentralPubMed Fruebis J, Tsao TS, Javorschi S, Ebbets-Reed D, Erickson MR, Yen FT, Bihain BE, Lodish HF (2001) Proteolytic cleavage product of 30-kDa adipocyte complement-related protein increases fatty acid oxidation in muscle and causes weight loss in mice. Proc Natl Acad Sci U S A 98:2005–2010CrossRefPubMedCentralPubMed
28.
go back to reference Kajimura D, Lee HW, Riley Kyle RJ, Arteaga-Solis E, Ferron M, Zhou B, Clarke CJ, Hannun YA, DePinho RA, Guo EX, Mann JJ, Karsenty G (2013) Adiponectin regulates bone mass via opposite central and peripheral mechanisms through FoxO1. Cell Metab 17:901–915CrossRefPubMedCentralPubMed Kajimura D, Lee HW, Riley Kyle RJ, Arteaga-Solis E, Ferron M, Zhou B, Clarke CJ, Hannun YA, DePinho RA, Guo EX, Mann JJ, Karsenty G (2013) Adiponectin regulates bone mass via opposite central and peripheral mechanisms through FoxO1. Cell Metab 17:901–915CrossRefPubMedCentralPubMed
29.
go back to reference Ferron M, Wei J, Yoshizawa T, Del Fattore A, DePinho RA, Teti A, Ducy P, Karsenty G (2010) Insulin signaling in osteoblasts integrates bone remodeling and energy metabolism. Cell 142:296–308CrossRefPubMedCentralPubMed Ferron M, Wei J, Yoshizawa T, Del Fattore A, DePinho RA, Teti A, Ducy P, Karsenty G (2010) Insulin signaling in osteoblasts integrates bone remodeling and energy metabolism. Cell 142:296–308CrossRefPubMedCentralPubMed
30.
go back to reference Schafer AL, Sellmeyer DE, Schwartz AV, Rosen CJ, Vittinghoff E, Palermo L, Bilezikian JP, Shoback DM, Black DM (2011) Change in undercarboxylated osteocalcin is associated with changes in body weight, fat mass, and adiponectin: parathyroid hormone (1–84) or alendronate therapy in postmenopausal women with osteoporosis (the PaTH study). J Clin Endocrinol Metab 96:E1982–E1989CrossRefPubMedCentralPubMed Schafer AL, Sellmeyer DE, Schwartz AV, Rosen CJ, Vittinghoff E, Palermo L, Bilezikian JP, Shoback DM, Black DM (2011) Change in undercarboxylated osteocalcin is associated with changes in body weight, fat mass, and adiponectin: parathyroid hormone (1–84) or alendronate therapy in postmenopausal women with osteoporosis (the PaTH study). J Clin Endocrinol Metab 96:E1982–E1989CrossRefPubMedCentralPubMed
31.
go back to reference Bozec A, Bakiri L, Jimenez M, Rosen ED, Catalá-Lehnen P, Schinke T, Schett G, Amling M, Wagner EF (2013) Osteoblast-specific expression of Fra-2/AP-1 controls Adiponectin/Osteocalcin expression and affects metabolism. J Cell Sci 126(23):5432–5440 Bozec A, Bakiri L, Jimenez M, Rosen ED, Catalá-Lehnen P, Schinke T, Schett G, Amling M, Wagner EF (2013) Osteoblast-specific expression of Fra-2/AP-1 controls Adiponectin/Osteocalcin expression and affects metabolism. J Cell Sci 126(23):5432–5440
32.
go back to reference Ituarte EA, Halstead LR, Iida-Klein A, Ituarte HG, Hahn TJ (1989) Glucose transport system in UMR-106-01 osteoblastic osteosarcoma cells: regulation by insulin. Calcif Tissue Int 45:27–33CrossRefPubMed Ituarte EA, Halstead LR, Iida-Klein A, Ituarte HG, Hahn TJ (1989) Glucose transport system in UMR-106-01 osteoblastic osteosarcoma cells: regulation by insulin. Calcif Tissue Int 45:27–33CrossRefPubMed
33.
go back to reference Kream BE, Smith MD, Canalis E, Raisz LG (1985) Characterization of the effect of insulin on collagen synthesis in fetal rat bone. Endocrinology 116:296–302CrossRefPubMed Kream BE, Smith MD, Canalis E, Raisz LG (1985) Characterization of the effect of insulin on collagen synthesis in fetal rat bone. Endocrinology 116:296–302CrossRefPubMed
34.
go back to reference Zhang W, Shen X, Wan C, Zhao Q, Zhang L, Zhou Q, Deng L (2012) Effects of insulin and insulin-like growth factor 1 on osteoblast proliferation and differentiation: differential signalling via Akt and ERK. Cell Biochem Funct 30:297–302CrossRefPubMed Zhang W, Shen X, Wan C, Zhao Q, Zhang L, Zhou Q, Deng L (2012) Effects of insulin and insulin-like growth factor 1 on osteoblast proliferation and differentiation: differential signalling via Akt and ERK. Cell Biochem Funct 30:297–302CrossRefPubMed
35.
go back to reference Fulzele K, Riddle RC, DiGirolamo DJ, Cao X, Wan C, Chen D, Faugere M-C, Aja S, Hussain MA, Brüning JC, Clemens TL (2010) Insulin receptor signaling in osteoblasts regulates postnatal bone acquisition and body composition. Cell 142:309–319CrossRefPubMedCentralPubMed Fulzele K, Riddle RC, DiGirolamo DJ, Cao X, Wan C, Chen D, Faugere M-C, Aja S, Hussain MA, Brüning JC, Clemens TL (2010) Insulin receptor signaling in osteoblasts regulates postnatal bone acquisition and body composition. Cell 142:309–319CrossRefPubMedCentralPubMed
36.
go back to reference Kops GJ, Dansen TB, Polderman PE, Saarloos I, Wirtz KW, Coffer PJ, Huang TT, Bos JL, Medema RH, Burgering BM (2002) Forkhead transcription factor FOXO3a protects quiescent cells from oxidative stress. Nature 419:316–321CrossRefPubMed Kops GJ, Dansen TB, Polderman PE, Saarloos I, Wirtz KW, Coffer PJ, Huang TT, Bos JL, Medema RH, Burgering BM (2002) Forkhead transcription factor FOXO3a protects quiescent cells from oxidative stress. Nature 419:316–321CrossRefPubMed
37.
go back to reference Medema RH, Kops GJPL, Bos JL, Burgering BMT (2000) AFX-like Forkhead transcription factors mediate cell-cycle regulation by Ras and PKB through p27kip1. Nature 404:782–787CrossRefPubMed Medema RH, Kops GJPL, Bos JL, Burgering BMT (2000) AFX-like Forkhead transcription factors mediate cell-cycle regulation by Ras and PKB through p27kip1. Nature 404:782–787CrossRefPubMed
38.
go back to reference Kode A, Mosialou I, Silva BC, Joshi S, Ferron M, Rached MT, Kousteni S (2012) FoxO1 protein cooperates with ATF4 protein in osteoblasts to control glucose homeostasis. J Biol Chem 287:8757–8768CrossRefPubMedCentralPubMed Kode A, Mosialou I, Silva BC, Joshi S, Ferron M, Rached MT, Kousteni S (2012) FoxO1 protein cooperates with ATF4 protein in osteoblasts to control glucose homeostasis. J Biol Chem 287:8757–8768CrossRefPubMedCentralPubMed
39.
go back to reference Almeida M, Han L, Martin-Millan M, O’Brien CA, Manolagas SC (2007) Oxidative stress antagonizes Wnt signaling in osteoblast precursors by diverting β-catenin from T cell Factor- to forkhead box O-mediated transcription. J Biol Chem 282:27298–27305CrossRefPubMed Almeida M, Han L, Martin-Millan M, O’Brien CA, Manolagas SC (2007) Oxidative stress antagonizes Wnt signaling in osteoblast precursors by diverting β-catenin from T cell Factor- to forkhead box O-mediated transcription. J Biol Chem 282:27298–27305CrossRefPubMed
40.
go back to reference Iyer S, Ambrogini E, Bartell SM, Han L, Roberson PK, de Cabo R, Jilka RL, Weinstein RS, O’Brien CA, Manolagas SC, Almeida M (2013) FOXOs attenuate bone formation by suppressing Wnt signaling. J Clin Invest 123:3409–3419CrossRefPubMedCentralPubMed Iyer S, Ambrogini E, Bartell SM, Han L, Roberson PK, de Cabo R, Jilka RL, Weinstein RS, O’Brien CA, Manolagas SC, Almeida M (2013) FOXOs attenuate bone formation by suppressing Wnt signaling. J Clin Invest 123:3409–3419CrossRefPubMedCentralPubMed
41.
go back to reference Poser JW, Price PA (1979) A method for decarboxylation of gamma-carboxyglutamic acid in proteins. properties of the decarboxylated gamma-carboxyglutamic acid protein from calf bone. J Biol Chem 254:431–436PubMed Poser JW, Price PA (1979) A method for decarboxylation of gamma-carboxyglutamic acid in proteins. properties of the decarboxylated gamma-carboxyglutamic acid protein from calf bone. J Biol Chem 254:431–436PubMed
42.
go back to reference Lacombe J, Karsenty G, Ferron M (2013) In vivo analysis of the contribution of bone resorption to the control of glucose metabolism in mice. Mol Metabol 2:498–504CrossRef Lacombe J, Karsenty G, Ferron M (2013) In vivo analysis of the contribution of bone resorption to the control of glucose metabolism in mice. Mol Metabol 2:498–504CrossRef
43.
go back to reference Wei J, Ferron M, Clarke CJ, Hannun YA, Jiang H, Blaner WS, Karsenty G (2014) Bone-specific insulin resistance disrupts whole-body glucose homeostasis via decreased osteocalcin activation. J Clin Invest 124:1–13CrossRefPubMed Wei J, Ferron M, Clarke CJ, Hannun YA, Jiang H, Blaner WS, Karsenty G (2014) Bone-specific insulin resistance disrupts whole-body glucose homeostasis via decreased osteocalcin activation. J Clin Invest 124:1–13CrossRefPubMed
44.
go back to reference Levinger I, Jerums G, Stepto NK, Parker L, Serpiello FR, McConell GK, Anderson M, Hare DL, Byrnes E, Ebeling PR, Seeman E (2014) The effect of acute exercise on undercarboxylated osteocalcin and insulin sensitivity in obese men. J Bone Miner Res. doi:10.1002/jbmr.2285 Levinger I, Jerums G, Stepto NK, Parker L, Serpiello FR, McConell GK, Anderson M, Hare DL, Byrnes E, Ebeling PR, Seeman E (2014) The effect of acute exercise on undercarboxylated osteocalcin and insulin sensitivity in obese men. J Bone Miner Res. doi:10.​1002/​jbmr.​2285
45.
go back to reference Hill HS, Grams J, Walton RG, Liu J, Moellering DR, Garvey WT (2014) Carboxylated and uncarboxylated forms of osteocalcin directly modulate the glucose transport system and inflammation in adipocytes. Horm Metab Res 46:341–347CrossRefPubMed Hill HS, Grams J, Walton RG, Liu J, Moellering DR, Garvey WT (2014) Carboxylated and uncarboxylated forms of osteocalcin directly modulate the glucose transport system and inflammation in adipocytes. Horm Metab Res 46:341–347CrossRefPubMed
47.
go back to reference Buttgereit F, Burmester GR, Straub RH, Seibel MJ, Zhou H (2011) Exogenous and endogenous glucocorticoids in rheumatic diseases. Arthritis Rheum 63:1–9CrossRefPubMed Buttgereit F, Burmester GR, Straub RH, Seibel MJ, Zhou H (2011) Exogenous and endogenous glucocorticoids in rheumatic diseases. Arthritis Rheum 63:1–9CrossRefPubMed
48.
go back to reference Buttgereit F, Doering G, Schaeffler A, Witte S, Sierakowski S, Gromnica-Ihle E, Jeka S, Krueger K, Szechinski J, Alten R (2008) Efficacy of modified-release versus standard prednisone to reduce duration of morning stiffness of the joints in rheumatoid arthritis (CAPRA-1): a double-blind, randomised controlled trial. Lancet 371:205–214CrossRefPubMed Buttgereit F, Doering G, Schaeffler A, Witte S, Sierakowski S, Gromnica-Ihle E, Jeka S, Krueger K, Szechinski J, Alten R (2008) Efficacy of modified-release versus standard prednisone to reduce duration of morning stiffness of the joints in rheumatoid arthritis (CAPRA-1): a double-blind, randomised controlled trial. Lancet 371:205–214CrossRefPubMed
49.
go back to reference Gounarides JS, Korach-André M, Killary K, Argentieri G, Turner O, Laurent D (2008) Effect of dexamethasone on glucose tolerance and fat metabolism in a diet-induced obesity mouse model. Endocrinology 149:758–766CrossRefPubMed Gounarides JS, Korach-André M, Killary K, Argentieri G, Turner O, Laurent D (2008) Effect of dexamethasone on glucose tolerance and fat metabolism in a diet-induced obesity mouse model. Endocrinology 149:758–766CrossRefPubMed
50.
go back to reference de Oliveira C, de Mattos A, Biz C, Oyama L, Ribeiro E, Oller do Nascimento C (2011) High-fat diet and glucocorticoid treatment cause hyperglycemia associated with adiponectin receptor alterations. Lipids Health Dis 10:11CrossRefPubMedCentralPubMed de Oliveira C, de Mattos A, Biz C, Oyama L, Ribeiro E, Oller do Nascimento C (2011) High-fat diet and glucocorticoid treatment cause hyperglycemia associated with adiponectin receptor alterations. Lipids Health Dis 10:11CrossRefPubMedCentralPubMed
51.
go back to reference Henneicke H, Herrmann M, Kalak R, Brennan-Speranza TC, Heinevetter U, Bertollo N, Day RE, Huscher D, Buttgereit F, Dunstan CR, Seibel MJ, Zhou H (2011) Corticosterone Selectively Targets endo-cortical surfaces by an osteoblast-dependent mechanism. Bone 49:733–742CrossRefPubMed Henneicke H, Herrmann M, Kalak R, Brennan-Speranza TC, Heinevetter U, Bertollo N, Day RE, Huscher D, Buttgereit F, Dunstan CR, Seibel MJ, Zhou H (2011) Corticosterone Selectively Targets endo-cortical surfaces by an osteoblast-dependent mechanism. Bone 49:733–742CrossRefPubMed
52.
go back to reference Oury F, Ferron M, Huizhen W, Confavreux C, Xu L, Lacombe J, Srinivas P, Chamouni A, Lugani F, Lejeune H, Kumar TR, Plotton I, Karsenty G (2013) Osteocalcin regulates murine and human fertility through a pancreas-bone-testis axis. J Clin Invest 123:2421–2433CrossRefPubMedCentralPubMed Oury F, Ferron M, Huizhen W, Confavreux C, Xu L, Lacombe J, Srinivas P, Chamouni A, Lugani F, Lejeune H, Kumar TR, Plotton I, Karsenty G (2013) Osteocalcin regulates murine and human fertility through a pancreas-bone-testis axis. J Clin Invest 123:2421–2433CrossRefPubMedCentralPubMed
53.
go back to reference Oury F, Sumara G, Sumara O, Ferron M, Chang H, Smith Charles E, Hermo L, Suarez S, Roth Bryan L, Ducy P, Karsenty G (2011) Endocrine regulation of male fertility by the skeleton. Cell 144:796–809CrossRefPubMedCentralPubMed Oury F, Sumara G, Sumara O, Ferron M, Chang H, Smith Charles E, Hermo L, Suarez S, Roth Bryan L, Ducy P, Karsenty G (2011) Endocrine regulation of male fertility by the skeleton. Cell 144:796–809CrossRefPubMedCentralPubMed
54.
go back to reference Pi M, Chen L, Huang MZ, Zhu W, Ringhofer B, Luo J, Christenson L, Li B, Zhang J, Jackson PD, Faber P, Brunden KR, Harrington JJ, Quarles LD (2008) GPRC6A null mice exhibit osteopenia, feminization and metabolic syndrome. PLoS One 3:e3858CrossRefPubMedCentralPubMed Pi M, Chen L, Huang MZ, Zhu W, Ringhofer B, Luo J, Christenson L, Li B, Zhang J, Jackson PD, Faber P, Brunden KR, Harrington JJ, Quarles LD (2008) GPRC6A null mice exhibit osteopenia, feminization and metabolic syndrome. PLoS One 3:e3858CrossRefPubMedCentralPubMed
55.
go back to reference Conigrave AD, Hampson DR (2010) Broad-spectrum amino acid-sensing class C G-protein coupled receptors: molecular mechanisms, physiological significance and options for drug development. Pharmacol Ther 127:252–260CrossRefPubMed Conigrave AD, Hampson DR (2010) Broad-spectrum amino acid-sensing class C G-protein coupled receptors: molecular mechanisms, physiological significance and options for drug development. Pharmacol Ther 127:252–260CrossRefPubMed
56.
go back to reference Bouschet T, Martin S, Henley JM (2012) Regulation of calcium sensing receptor trafficking by RAMPs. Adv Exp Med Biol 744:39–48CrossRefPubMed Bouschet T, Martin S, Henley JM (2012) Regulation of calcium sensing receptor trafficking by RAMPs. Adv Exp Med Biol 744:39–48CrossRefPubMed
58.
go back to reference Pi M, Faber P, Ekema G, Jackson PD, Ting A, Wang N, Fontilla-Poole M, Mays RW, Brunden KR, Harrington JJ, Quarles LD (2005) Identification of a novel extracellular cation-sensing G-protein-coupled receptor. J Biol Chem 280:40201–40209CrossRefPubMedCentralPubMed Pi M, Faber P, Ekema G, Jackson PD, Ting A, Wang N, Fontilla-Poole M, Mays RW, Brunden KR, Harrington JJ, Quarles LD (2005) Identification of a novel extracellular cation-sensing G-protein-coupled receptor. J Biol Chem 280:40201–40209CrossRefPubMedCentralPubMed
59.
go back to reference Pi M, Wu Y, Quarles LD (2011) GPRC6A mediates responses to osteocalcin in β-cells in vitro and pancreas in vivo. J Bone Miner Res 26:1680–1683CrossRefPubMed Pi M, Wu Y, Quarles LD (2011) GPRC6A mediates responses to osteocalcin in β-cells in vitro and pancreas in vivo. J Bone Miner Res 26:1680–1683CrossRefPubMed
60.
go back to reference Jacobsen SE, Norskov-Lauritsen L, Thomsen AR, Smajilovic S, Wellendorph P, Larsson NH, Lehmann A, Bhatia VK, Brauner-Osborne H (2013) Delineation of the GPRC6A receptor signaling pathways using a mammalian cell line stably expressing the receptor. J Pharmacol Exp Ther 347:298–309CrossRefPubMed Jacobsen SE, Norskov-Lauritsen L, Thomsen AR, Smajilovic S, Wellendorph P, Larsson NH, Lehmann A, Bhatia VK, Brauner-Osborne H (2013) Delineation of the GPRC6A receptor signaling pathways using a mammalian cell line stably expressing the receptor. J Pharmacol Exp Ther 347:298–309CrossRefPubMed
61.
go back to reference Wei J, Hanna T, Suda N, Karsenty G, Ducy P (2014) Osteocalcin promotes β-cell proliferation during development and adulthood through GPRC6A. Diabetes 63:1021–1031CrossRefPubMedCentralPubMed Wei J, Hanna T, Suda N, Karsenty G, Ducy P (2014) Osteocalcin promotes β-cell proliferation during development and adulthood through GPRC6A. Diabetes 63:1021–1031CrossRefPubMedCentralPubMed
62.
go back to reference Wellendorph P, Johansen LD, Jensen AA, Casanova E, Gassmann M, Deprez P, Clément-Lacroix P, Bettler B, Bräuner-Osborne H (2009) No evidence for a bone phenotype in GPRC6A knockout mice under normal physiological conditions. J Mol Endocrinol 42:215–223CrossRefPubMed Wellendorph P, Johansen LD, Jensen AA, Casanova E, Gassmann M, Deprez P, Clément-Lacroix P, Bettler B, Bräuner-Osborne H (2009) No evidence for a bone phenotype in GPRC6A knockout mice under normal physiological conditions. J Mol Endocrinol 42:215–223CrossRefPubMed
63.
go back to reference Smajilovic S, Clemmensen C, Johansen L, Wellendorph P, Holst J, Thams P, Ogo E, Bräuner-Osborne H (2013) The l-α-amino acid receptor GPRC6A is expressed in the islets of Langerhans but is not involved in l-arginine-induced insulin release. Amino Acids 44:383–390CrossRefPubMed Smajilovic S, Clemmensen C, Johansen L, Wellendorph P, Holst J, Thams P, Ogo E, Bräuner-Osborne H (2013) The l-α-amino acid receptor GPRC6A is expressed in the islets of Langerhans but is not involved in l-arginine-induced insulin release. Amino Acids 44:383–390CrossRefPubMed
64.
go back to reference Clemmensen C, Smajilovic S, Madsen AN, Klein AB, Holst B, Bräuner-Osborne H (2013) Increased susceptibility to diet-induced obesity in GPRC6A receptor knockout mice. J Endocrinol 217:151–160CrossRefPubMed Clemmensen C, Smajilovic S, Madsen AN, Klein AB, Holst B, Bräuner-Osborne H (2013) Increased susceptibility to diet-induced obesity in GPRC6A receptor knockout mice. J Endocrinol 217:151–160CrossRefPubMed
65.
go back to reference Clemmensen C, Pehmoller C, Klein AB, Ratner C, Wojtaszewski JF, Brauner-Osborne H (2013) Enhanced voluntary wheel running in GPRC6A receptor knockout mice. Physiol Behav 118:144–151CrossRefPubMed Clemmensen C, Pehmoller C, Klein AB, Ratner C, Wojtaszewski JF, Brauner-Osborne H (2013) Enhanced voluntary wheel running in GPRC6A receptor knockout mice. Physiol Behav 118:144–151CrossRefPubMed
66.
go back to reference Desjardins C (1978) Endocrine regulation of reproductive development and function in the male. J Anim Sci 47(Suppl 2):56–79PubMed Desjardins C (1978) Endocrine regulation of reproductive development and function in the male. J Anim Sci 47(Suppl 2):56–79PubMed
67.
go back to reference Dorrington JH, Armstrong DT (1979) Effects of FSH on gonadal functions. Recent Prog Horm Res 35:301–342PubMed Dorrington JH, Armstrong DT (1979) Effects of FSH on gonadal functions. Recent Prog Horm Res 35:301–342PubMed
68.
go back to reference Oury F, Khrimian L, Denny CA, Gardin A, Chamouni A, Goeden N, Huang YY, Lee H, Srinivas P, Gao XB, Suyama S, Langer T, Mann JJ, Horvath TL, Bonnin A, Karsenty G (2013) Maternal and offspring pools of osteocalcin influence brain development and functions. Cell 155:228–241CrossRefPubMed Oury F, Khrimian L, Denny CA, Gardin A, Chamouni A, Goeden N, Huang YY, Lee H, Srinivas P, Gao XB, Suyama S, Langer T, Mann JJ, Horvath TL, Bonnin A, Karsenty G (2013) Maternal and offspring pools of osteocalcin influence brain development and functions. Cell 155:228–241CrossRefPubMed
69.
go back to reference Kapustin AN, Shanahan CM (2011) Osteocalcin: a novel vascular metabolic and osteoinductive factor? Arterioscler Thromb Vasc Biol 31:2169–2171CrossRefPubMed Kapustin AN, Shanahan CM (2011) Osteocalcin: a novel vascular metabolic and osteoinductive factor? Arterioscler Thromb Vasc Biol 31:2169–2171CrossRefPubMed
70.
go back to reference Shanahan CM, Cary NRB, Salisbury JR, Proudfoot D, Weissberg PL, Edmonds ME (1999) Medial localization of mineralization-regulating proteins in association with Mönckeberg’s sclerosis: evidence for smooth muscle cell-mediated vascular calcification. Circulation 100:2168–2176CrossRefPubMed Shanahan CM, Cary NRB, Salisbury JR, Proudfoot D, Weissberg PL, Edmonds ME (1999) Medial localization of mineralization-regulating proteins in association with Mönckeberg’s sclerosis: evidence for smooth muscle cell-mediated vascular calcification. Circulation 100:2168–2176CrossRefPubMed
71.
go back to reference Proudfoot D, Davies JD, Skepper JN, Weissberg PL, Shanahan CM (2002) Acetylated low-density lipoprotein stimulates human vascular smooth muscle cell calcification by promoting osteoblastic differentiation and inhibiting phagocytosis. Circulation 106:3044–3050CrossRefPubMed Proudfoot D, Davies JD, Skepper JN, Weissberg PL, Shanahan CM (2002) Acetylated low-density lipoprotein stimulates human vascular smooth muscle cell calcification by promoting osteoblastic differentiation and inhibiting phagocytosis. Circulation 106:3044–3050CrossRefPubMed
72.
go back to reference Tyson KL, Reynolds JL, McNair R, Zhang Q, Weissberg PL, Shanahan CM (2003) Osteo/chondrocytic transcription factors and their target genes exhibit distinct patterns of expression in human arterial calcification. Arterioscler Thromb Vasc Biol 23:489–494CrossRefPubMed Tyson KL, Reynolds JL, McNair R, Zhang Q, Weissberg PL, Shanahan CM (2003) Osteo/chondrocytic transcription factors and their target genes exhibit distinct patterns of expression in human arterial calcification. Arterioscler Thromb Vasc Biol 23:489–494CrossRefPubMed
73.
go back to reference Idelevich A, Rais Y, Monsonego-Ornan E (2011) Bone Gla protein increases HIF-1α-dependent glucose metabolism and induces cartilage and vascular calcification. Arterioscl Thromb Vasc Biol 31:e55–e71CrossRefPubMed Idelevich A, Rais Y, Monsonego-Ornan E (2011) Bone Gla protein increases HIF-1α-dependent glucose metabolism and induces cartilage and vascular calcification. Arterioscl Thromb Vasc Biol 31:e55–e71CrossRefPubMed
74.
go back to reference Finlay DK, Rosenzweig E, Sinclair LV, Feijoo-Carnero C, Hukelmann JL, Rolf J, Panteleyev AA, Okkenhaug K, Cantrell DA (2012) PDK1 regulation of mTOR and hypoxia-inducible factor 1 integrate metabolism and migration of CD8+ T cells. J Exp Med 209:2441–2453CrossRefPubMedCentralPubMed Finlay DK, Rosenzweig E, Sinclair LV, Feijoo-Carnero C, Hukelmann JL, Rolf J, Panteleyev AA, Okkenhaug K, Cantrell DA (2012) PDK1 regulation of mTOR and hypoxia-inducible factor 1 integrate metabolism and migration of CD8+ T cells. J Exp Med 209:2441–2453CrossRefPubMedCentralPubMed
76.
go back to reference Kanazawa I, Yamaguchi T, Tada Y, Yamauchi M, Yano S, Sugimoto T (2011) Serum osteocalcin level is positively associated with insulin sensitivity and secretion in patients with type 2 diabetes. Bone 48:720–725CrossRefPubMed Kanazawa I, Yamaguchi T, Tada Y, Yamauchi M, Yano S, Sugimoto T (2011) Serum osteocalcin level is positively associated with insulin sensitivity and secretion in patients with type 2 diabetes. Bone 48:720–725CrossRefPubMed
77.
go back to reference Inaba M, Nishizawa Y, Mita K, Kumeda Y, Emoto M, Kawagishi T, Ishimura E, Nakatsuka K, Shioi A, Morii H (1999) Poor glycemic control impairs the response of biochemical parameters of bone formation and resorption to exogenous 1,25-dihydroxyvitamin D3 in patients with type 2 diabetes. Osteoporos Int 9:525–531CrossRefPubMed Inaba M, Nishizawa Y, Mita K, Kumeda Y, Emoto M, Kawagishi T, Ishimura E, Nakatsuka K, Shioi A, Morii H (1999) Poor glycemic control impairs the response of biochemical parameters of bone formation and resorption to exogenous 1,25-dihydroxyvitamin D3 in patients with type 2 diabetes. Osteoporos Int 9:525–531CrossRefPubMed
78.
go back to reference Pittas AG, Harris SS, Eliades M, Stark P, Dawson-Hughes B (2009) Association between serum osteocalcin and markers of metabolic phenotype. J Clin Endocrinol Metab 94:827–832CrossRefPubMedCentralPubMed Pittas AG, Harris SS, Eliades M, Stark P, Dawson-Hughes B (2009) Association between serum osteocalcin and markers of metabolic phenotype. J Clin Endocrinol Metab 94:827–832CrossRefPubMedCentralPubMed
79.
go back to reference Kindblom JM, Ohlsson C, Ljunggren O, Karlsson MK, Tivesten A, Smith U, Mellstrom D (2009) Plasma osteocalcin is inversely related to fat mass and plasma glucose in elderly Swedish men. J Bone Miner Res 24:785–791CrossRefPubMed Kindblom JM, Ohlsson C, Ljunggren O, Karlsson MK, Tivesten A, Smith U, Mellstrom D (2009) Plasma osteocalcin is inversely related to fat mass and plasma glucose in elderly Swedish men. J Bone Miner Res 24:785–791CrossRefPubMed
80.
go back to reference Gravenstein KS, Napora JK, Short RG, Ramachandran R, Carlson OD, Metter EJ, Ferrucci L, Egan JM, Chia CW (2011) Cross-sectional evidence of a signaling pathway from bone homeostasis to glucose metabolism. J Clin Endocrinol Metab 96:E884–E890CrossRefPubMedCentralPubMed Gravenstein KS, Napora JK, Short RG, Ramachandran R, Carlson OD, Metter EJ, Ferrucci L, Egan JM, Chia CW (2011) Cross-sectional evidence of a signaling pathway from bone homeostasis to glucose metabolism. J Clin Endocrinol Metab 96:E884–E890CrossRefPubMedCentralPubMed
81.
go back to reference Sayinalp S, Gedik O, Koray Z (1995) Increasing serum osteocalcin after glycemic control in diabetic men. Calcif Tissue Int 57:422–425CrossRefPubMed Sayinalp S, Gedik O, Koray Z (1995) Increasing serum osteocalcin after glycemic control in diabetic men. Calcif Tissue Int 57:422–425CrossRefPubMed
82.
go back to reference Lu C, Ivaska KK, Alen M, Wang Q, Tormakangas T, Xu L, Wiklund P, Mikkola TM, Pekkala S, Tian H, Vaananen HK, Cheng S (2012) Serum osteocalcin is not associated with glucose but is inversely associated with leptin across generations of nondiabetic women. J Clin Endocrinol Metab 97:4106–4114CrossRefPubMed Lu C, Ivaska KK, Alen M, Wang Q, Tormakangas T, Xu L, Wiklund P, Mikkola TM, Pekkala S, Tian H, Vaananen HK, Cheng S (2012) Serum osteocalcin is not associated with glucose but is inversely associated with leptin across generations of nondiabetic women. J Clin Endocrinol Metab 97:4106–4114CrossRefPubMed
83.
go back to reference Osorio J (2012) Metabolism: no role for osteocalcin in glucose metabolism-challenging a paradigm? Nat Rev Endocrinol 8:626CrossRefPubMed Osorio J (2012) Metabolism: no role for osteocalcin in glucose metabolism-challenging a paradigm? Nat Rev Endocrinol 8:626CrossRefPubMed
84.
go back to reference von Mach MA, Stoeckli R, Bilz S, Kraenzlin M, Langer I, Keller U (2004) Changes in bone mineral content after surgical treatment of morbid obesity. Metabolism 53:918–921CrossRef von Mach MA, Stoeckli R, Bilz S, Kraenzlin M, Langer I, Keller U (2004) Changes in bone mineral content after surgical treatment of morbid obesity. Metabolism 53:918–921CrossRef
85.
go back to reference Garcia-Martin A, Cortes-Berdonces M, Luque-Fernandez I, Rozas-Moreno P, Quesada-Charneco M, Munoz-Torres M (2011) Osteocalcin as a marker of metabolic risk in healthy postmenopausal women. Menopause 18:537–541CrossRefPubMed Garcia-Martin A, Cortes-Berdonces M, Luque-Fernandez I, Rozas-Moreno P, Quesada-Charneco M, Munoz-Torres M (2011) Osteocalcin as a marker of metabolic risk in healthy postmenopausal women. Menopause 18:537–541CrossRefPubMed
86.
go back to reference Yeap BB, Chubb SA, Flicker L, McCaul KA, Ebeling PR, Beilby JP, Norman PE (2010) Reduced serum total osteocalcin is associated with metabolic syndrome in older men via waist circumference, hyperglycemia, and triglyceride levels. Eur J Endocrinol 163:265–272CrossRefPubMed Yeap BB, Chubb SA, Flicker L, McCaul KA, Ebeling PR, Beilby JP, Norman PE (2010) Reduced serum total osteocalcin is associated with metabolic syndrome in older men via waist circumference, hyperglycemia, and triglyceride levels. Eur J Endocrinol 163:265–272CrossRefPubMed
87.
go back to reference Levinger I, Zebaze R, Jerums G, Hare DL, Selig S, Seeman E (2011) The effect of acute exercise on undercarboxylated osteocalcin in obese men. Osteoporos Int 22:1621–1626CrossRefPubMed Levinger I, Zebaze R, Jerums G, Hare DL, Selig S, Seeman E (2011) The effect of acute exercise on undercarboxylated osteocalcin in obese men. Osteoporos Int 22:1621–1626CrossRefPubMed
88.
go back to reference Schafer AL, Sellmeyer DE, Schwartz AV, Rosen CJ, Vittinghoff E, Palermo L, Bilezikian JP, Shoback DM, Black DM (2011) Change in undercarboxylated osteocalcin is associated with changes in body weight, fat mass, and adiponectin: parathyroid hormone (1–84) or alendronate therapy in postmenopausal women with osteoporosis (the PaTH study). J Clin Endocrinol Metab 96:E1982–E1989CrossRefPubMedCentralPubMed Schafer AL, Sellmeyer DE, Schwartz AV, Rosen CJ, Vittinghoff E, Palermo L, Bilezikian JP, Shoback DM, Black DM (2011) Change in undercarboxylated osteocalcin is associated with changes in body weight, fat mass, and adiponectin: parathyroid hormone (1–84) or alendronate therapy in postmenopausal women with osteoporosis (the PaTH study). J Clin Endocrinol Metab 96:E1982–E1989CrossRefPubMedCentralPubMed
89.
go back to reference Kanazawa I, Yamaguchi T, Yamauchi M, Yamamoto M, Kurioka S, Yano S, Sugimoto T (2011) Serum undercarboxylated osteocalcin was inversely associated with plasma glucose level and fat mass in type 2 diabetes mellitus. Osteoporos Int 22:187–194CrossRefPubMed Kanazawa I, Yamaguchi T, Yamauchi M, Yamamoto M, Kurioka S, Yano S, Sugimoto T (2011) Serum undercarboxylated osteocalcin was inversely associated with plasma glucose level and fat mass in type 2 diabetes mellitus. Osteoporos Int 22:187–194CrossRefPubMed
90.
go back to reference Pollock NK, Bernard PJ, Gower BA, Gundberg CM, Wenger K, Misra S, Bassali RW, Davis CL (2011) Lower uncarboxylated osteocalcin concentrations in children with prediabetes is associated with beta-cell function. J Clin Endocrinol Metab 96:E1092–E1099CrossRefPubMedCentralPubMed Pollock NK, Bernard PJ, Gower BA, Gundberg CM, Wenger K, Misra S, Bassali RW, Davis CL (2011) Lower uncarboxylated osteocalcin concentrations in children with prediabetes is associated with beta-cell function. J Clin Endocrinol Metab 96:E1092–E1099CrossRefPubMedCentralPubMed
91.
go back to reference Iki M, Tamaki J, Fujita Y, Kouda K, Yura A, Kadowaki E, Sato Y, Moon JS, Tomioka K, Okamoto N, Kurumatani N (2012) Serum undercarboxylated osteocalcin levels are inversely associated with glycemic status and insulin resistance in an elderly Japanese male population: Fujiwara-kyo Osteoporosis Risk in Men (FORMEN) Study. Osteoporos Int 23:761–770CrossRefPubMed Iki M, Tamaki J, Fujita Y, Kouda K, Yura A, Kadowaki E, Sato Y, Moon JS, Tomioka K, Okamoto N, Kurumatani N (2012) Serum undercarboxylated osteocalcin levels are inversely associated with glycemic status and insulin resistance in an elderly Japanese male population: Fujiwara-kyo Osteoporosis Risk in Men (FORMEN) Study. Osteoporos Int 23:761–770CrossRefPubMed
92.
go back to reference 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 Metabol Res Rev 25:768–772CrossRef 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 Metabol Res Rev 25:768–772CrossRef
93.
go back to reference Confavreux CB, Borel O, Lee F, Vaz G, Guyard M, Fadat C, Carlier MC, Chapurlat R, Karsenty G (2012) Osteoid osteoma is an osteocalcinoma affecting glucose metabolism. Osteoporos Int 23:1645–1650CrossRefPubMed Confavreux CB, Borel O, Lee F, Vaz G, Guyard M, Fadat C, Carlier MC, Chapurlat R, Karsenty G (2012) Osteoid osteoma is an osteocalcinoma affecting glucose metabolism. Osteoporos Int 23:1645–1650CrossRefPubMed
Metadata
Title
Osteocalcin: An Osteoblast-Derived Polypeptide Hormone that Modulates Whole Body Energy Metabolism
Authors
Tara C. Brennan-Speranza
Arthur D. Conigrave
Publication date
01-01-2015
Publisher
Springer US
Published in
Calcified Tissue International / Issue 1/2015
Print ISSN: 0171-967X
Electronic ISSN: 1432-0827
DOI
https://doi.org/10.1007/s00223-014-9931-y

Other articles of this Issue 1/2015

Calcified Tissue International 1/2015 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine