11β-Hydroxysteroid Dehydrogenase Expression and Glucocorticoid Synthesis Are Directed by a Molecular Switch during Osteoblast Differentiation

The Endocrine Society - Tập 19 Số 3 - Trang 621-631 - 2005
Marco Eijken1, Martin Hewison2, Mark S. Cooper2, Frank H. de Jong1, Hideki Chiba3, Paul M. Stewart2, André G. Uitterlinden1, Huibert A. P. Pols1, Johannes P.T.M. van Leeuwen1
1Department of Internal Medicine (M.E., F.H.d.J., A.G.U., H.A.P.P., J.P.T.M.v.L.), Erasmus Medical Centre, 3000 DR Rotterdam, The Netherlands;
2Division of Medical Science (M.H., M.S.C., P.M.S.), Institute of Biomedical Research, The University of Birmingham, Birmingham B15 2TT, United Kingdom;
3Department of Pathology (H.C.), Sapporo Medical College, Sapporo 060-8556, Japan

Tóm tắt

Abstract11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1) plays an important role in the prereceptor regulation of corticosteroids by locally converting cortisone into active cortisol. To investigate the impact of this mechanism on osteoblast development, we have characterized 11β-HSD1 activity and regulation in a differentiating human osteoblast cell line (SV-HFO). Continuous treatment with the synthetic glucocorticoid dexamethasone induces differentiation of SV-HFO cells during 21 d of culture. Using this cell system, we showed an inverse relationship between 11β-HSD1 activity and osteoblast differentiation. 11β-HSD1 mRNA expression and activity were low and constant in differentiating osteoblasts. However, in the absence of differentiation (no dexamethasone), 11β-HSD1 mRNA and activity increased strongly from d 12 of culture onward, with a peak around d 19. Promoter reporter studies provided evidence that specific regions of the 11β-HSD1 gene are involved in this differentiation controlled regulation of the enzyme. Functional implication of these changes in 11β-HSD1 is shown by the induction of osteoblast differentiation in the presence of cortisone. The current study demonstrates the presence of an intrinsic differentiation-driven molecular switch that controls expression and activity of 11β-HSD1 and thereby cortisol production by human osteoblasts. This efficient mechanism by which osteoblasts generate cortisol in an autocrine fashion to ensure proper differentiation will help to understand the complex effects of cortisol on bone metabolism.

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Tài liệu tham khảo

Cheng, 1996, Expression of bone matrix proteins during dexamethasone-induced mineralization of human bone marrow stromal cells., J Cell Biochem, 61, 182, 10.1002/(SICI)1097-4644(19960501)61:2<182::AID-JCB3>3.0.CO;2-Q

Iba, 1995, Glucocorticoids induce mineralization coupled with bone protein expression without influence on growth of a human osteoblastic cell line., Cell Struct Funct, 20, 319, 10.1247/csf.20.319

Herbertson, 1995, Dexamethasone alters the subpopulation make-up of rat bone marrow stromal cell cultures., J Bone Miner Res, 10, 285, 10.1002/jbmr.5650100216

Weinstein, 1998, Inhibition of osteoblastogenesis and promotion of apoptosis of osteoblasts and osteocytes by glucocorticoids. Potential mechanisms of their deleterious effects on bone., J Clin Invest, 102, 274, 10.1172/JCI2799

Weinstein, 2001, Glucocorticoid-induced osteoporosis., Rev Endocr Metab Disord, 2, 65, 10.1023/A:1010007108155

Canalis, 1996, Clinical review 83: Mechanisms of glucocorticoid action in bone: implications to glucocorticoid-induced osteoporosis., J Clin Endocrinol Metab, 81, 3441

Hirayama, 2002, Effect of corticosteroids on human osteoclast formation and activity., J Endocrinol, 175, 155, 10.1677/joe.0.1750155

Pockwinse, 1995, Developmental stage-specific cellular responses to vitamin D and glucocorticoids during differentiation of the osteoblast phenotype: interrelationship of morphology and gene expression by in situ hybridization., Exp Cell Res, 216, 244, 10.1006/excr.1995.1031

Smith, 2000, Glucocorticoids inhibit developmental stage-specific osteoblast cell cycle. Dissociation of cyclin A-cyclin-dependent kinase 2 from E2F4–p130 complexes., J Biol Chem, 275, 19992, 10.1074/jbc.M001758200

Ishida, 1998, Glucocorticoid-induced osteoporosis: both in vivo and in vitro concentrations of glucocorticoids higher than physiological levels attenuate osteoblast differentiation., J Bone Miner Res, 13, 1822, 10.1359/jbmr.1998.13.12.1822

Liesegang, 1994, Human osteoblast-like cells contain specific, saturable, high-affinity glucocorticoid, androgen, estrogen, and 1α,25-dihydroxycholecalciferol receptors., J Androl, 15, 194, 10.1002/j.1939-4640.1994.tb00430.x

Heinrichs, 1993, Identification of multiple glucocorticoid receptor binding sites in the rat osteocalcin gene promoter., Biochemistry, 32, 11436, 10.1021/bi00093a022

Peterkofsky, 1999, Species differences in cis-elements of the proα1(I) procollagen promoter and their binding proteins., J Cell Biochem, 73, 408, 10.1002/(SICI)1097-4644(19990601)73:3<408::AID-JCB12>3.0.CO;2-D

Parrelli, 1998, Identification of a glucocorticoid response element in the human transforming growth factor β1 gene promoter., Int J Biochem Cell Biol, 30, 623, 10.1016/S1357-2725(98)00005-3

Schmidt, 1994, Autoregulation of corticosteroid receptors. How, when, where, and why?, Receptor, 4, 229

Kino, 2003, Tissue glucocorticoid resistance/hypersensitivity syndromes., J Steroid Biochem Mol Biol, 85, 457, 10.1016/S0960-0760(03)00218-8

Stewart, 1999, 11β-Hydroxysteroid dehydrogenase., Vitam Horm, 57, 249, 10.1016/S0083-6729(08)60646-9

Tannin, 1991, The human gene for 11β-hydroxysteroid dehydrogenase. Structure, tissue distribution, and chromosomal localization., J Biol Chem, 266, 16653, 10.1016/S0021-9258(18)55351-5

Seckl, 2001, Minireview: 11β-hydroxysteroid dehydrogenase type 1—a tissue-specific amplifier of glucocorticoid action., Endocrinology, 142, 1371, 10.1210/endo.142.4.8114

Albiston, 1994, Cloning and tissue distribution of the human 11β-hydroxysteroid dehydrogenase type 2 enzyme., Mol Cell Endocrinol, 105, R11, 10.1016/0303-7207(94)90176-7

Edwards, 1988, Localisation of 11β-hydroxysteroid dehydrogenase—tissue specific protector of the mineralocorticoid receptor., Lancet, 2, 986, 10.1016/S0140-6736(88)90742-8

Bland, 1999, Characterization of 11β-hydroxysteroid dehydrogenase activity and corticosteroid receptor expression in human osteosarcoma cell lines., J Endocrinol, 161, 455, 10.1677/joe.0.1610455

Cooper, 2000, Expression and functional consequences of 11β-hydroxysteroid dehydrogenase activity in human bone., Bone, 27, 375, 10.1016/S8756-3282(00)00344-6

Cooper, 1999, Glucocorticoid activity, inactivity and the osteoblast., J Endocrinol, 163, 159, 10.1677/joe.0.1630159

Canalis, 2002, 11β-Hydroxysteroid dehydrogenase, an amplifier of glucocorticoid action in osteoblasts., J Bone Miner Res, 17, 987, 10.1359/jbmr.2002.17.6.987

Cooper, 2002, Osteoblastic 11β-hydroxysteroid dehydrogenase type 1 activity increases with age and glucocorticoid exposure., J Bone Miner Res, 17, 979, 10.1359/jbmr.2002.17.6.979

Cooper, 2003, 11β-Hydroxysteroid dehydrogenase type 1 activity predicts the effects of glucocorticoids on bone., J Clin Endocrinol Metab, 88, 3874, 10.1210/jc.2003-022025

Liu, 1996, Effect of growth hormone, insulin and dexamethasone on 11β-hydroxysteroid dehydrogenase activity on a primary culture of rat hepatocytes., Life Sci, 59, 227, 10.1016/0024-3205(96)00288-3

Bujalska, 1999, Differentiation of adipose stromal cells: the roles of glucocorticoids and 11β-hydroxysteroid dehydrogenase., Endocrinology, 140, 3188, 10.1210/endo.140.7.6868

Hammami, 1991, Regulation of 11β-hydroxysteroid dehydrogenase activity in human skin fibroblasts: enzymatic modulation of glucocorticoid action., J Clin Endocrinol Metab, 73, 326, 10.1210/jcem-73-2-326

Jamieson, 1999, Tissue- and temporal-specific regulation of 11β-hydroxysteroid dehydrogenase type 1 by glucocorticoids in vivo., J Steroid Biochem Mol Biol, 68, 245, 10.1016/S0960-0760(99)00037-0

Shen, 2002, Histone acetylation in vivo at the osteocalcin locus is functionally linked to vitamin D-dependent, bone tissue-specific transcription., J Biol Chem, 277, 20284, 10.1074/jbc.M112440200

Lian, 2003, The temporal and spatial subnuclear organization of skeletal gene regulatory machinery: integrating multiple levels of transcriptional control., Calcif Tissue Int, 72, 631, 10.1007/s00223-002-1058-x

Williams, 2000, C/EBP regulates hepatic transcription of 11β -hydroxysteroid dehydrogenase type 1. A novel mechanism for cross-talk between the C/EBP and glucocorticoid signaling pathways., J Biol Chem, 275, 30232, 10.1074/jbc.M001286200

Delany, 2001, Glucocorticoid suppression of IGF I transcription in osteoblasts., Mol Endocrinol, 15, 1781, 10.1210/mend.15.10.0704

Pereira, 2002, Effects of cortisol and bone morphogenetic protein-2 on stromal cell differentiation: correlation with CCAAT-enhancer binding protein expression., Bone, 30, 685, 10.1016/S8756-3282(02)00687-7

Wake, 2004, 11β-Hydroxysteroid dehydrogenase type 1 in obesity and the metabolic syndrome., Mol Cell Endocrinol, 215, 45, 10.1016/j.mce.2003.11.015

Bujalska, 2002, A switch in dehydrogenase to reductase activity of 11β-hydroxysteroid dehydrogenase type 1 upon differentiation of human omental adipose stromal cells., J Clin Endocrinol Metab, 87, 1205

Dunn, 1981, Transport of steroid hormones: binding of 21 endogenous steroids to both testosterone-binding globulin and corticosteroid-binding globulin in human plasma., J Clin Endocrinol Metab, 53, 58, 10.1210/jcem-53-1-58

Gruber, 2002, Production and actions of estrogens., N Engl J Med, 346, 340, 10.1056/NEJMra000471

Janssen, 1999, Estradiol formation by human osteoblasts via multiple pathways: relation with osteoblast function., J Cell Biochem, 75, 528, 10.1002/(SICI)1097-4644(19991201)75:3<528::AID-JCB16>3.0.CO;2-3

Justesen, 2004, Mice deficient in 11β-hydroxysteroid dehydrogenase type 1 lack bone marrow adipocytes, but maintain normal bone formation., Endocrinology, 145, 1916, 10.1210/en.2003-1427

Sher, 2004, Transgenic expression of 11β-hydroxysteroid dehydrogenase type 2 in osteoblasts reveals an anabolic role for endogenous glucocorticoids in bone., Endocrinology, 145, 922, 10.1210/en.2003-0655

Chiba, 1993, Establishment and characterization of a simian virus 40-immortalized osteoblastic cell line from normal human bone., Jpn J Cancer Res, 84, 290, 10.1111/j.1349-7006.1993.tb02869.x

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The Endocrine Society

Tập 19 Số 3

621-631

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