Species-specific glucocorticoid and 1,25-dihydroxyvitamin D responsiveness in mouse MC3T3–E1 osteoblasts: dexamethasone inhibits osteoblast differentiation and vitamin D down-regulates osteocalcin gene expression.

Lian, Jane B.; Shalhoub, Victoria; Aslam, Fauzia; Frenkel, Baruch; Green, Jack; Hamrah, Michael; Stein, Gary S.; Stein, Janet L.

doi:10.1210/endo.138.5.5117

Cited by 154Bone Metabolism and DiseasesVitamin D Research StudiesBone health and osteoporosis research

Species-specific glucocorticoid and 1,25-dihydroxyvitamin D responsiveness in mouse MC3T3–E1 osteoblasts: dexamethasone inhibits osteoblast differentiation and vitamin D down-regulates osteocalcin gene expression.

Lian, Jane B., Shalhoub, Victoria, Aslam, Fauzia, Frenkel, Baruch, Green, Jack, Hamrah, Michael, Stein, Gary S., Stein, Janet L.·1997·Endocrinology

DOI 10.1210/endo.138.5.5117

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Abstract

The mouse MC3T3-E1 cell line is nontumorigenic and undergoes a typical program of osteoblast differentiation in vitro, producing a bone-like mineralized extracellular matrix. We report responses of these cells to dexamethasone (Dex) and 1,25-(OH)2D3 that are in contrast to findings from other osteoblast culture systems. First, chronic exposure of both early- and late-passaged MC3T3-E1 cells to 10(-7) M Dex, initiated during the proliferation period, blocked osteoblast differentiation, in contrast to the enhanced differentiation observed in cultures of fetal rat calvarial-derived cells. Secondly, 1,25-(OH)2D3 did not up-regulate expression (messenger RNA or protein synthesis) of the endogenous mouse osteocalcin (OC) gene. Several lines of evidence are presented that suggest this response is caused by sequence specific properties of the mouse OC vitamin D response element. We also observed both qualitative and quantitative differences in expression of cell growth (histone H2B) and phenotype-related genes (collagen, OC, osteopontin, glucocorticoid receptor, and 1, 25-(OH)2D3 receptor), between pre- and postmineralization stage osteoblasts, in response to 24 h steroid hormone treatment. Our findings in MC3T3-E1 cells are consistent with current concepts of selective influences of 1,25-(OH)2D3 and glucocorticoids as a function of osteoblast maturation. However, the inhibition of osteoblast differentiation by chronic Dex at 10(-7) M and the down-regulation of OC by 1,25-(OH)2D3 are novel observations relevant to species-specific responsiveness of mouse bone-expressed genes to steroid hormones during osteoblast differentiation.

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“Vitamin D does not mediate enhanced activity of the mouse OC promoter (70), and in fact, the mouse OC VDRE exhibits weak downregulation by the hormone (39).”
BackgroundSelf-citation
Human Osteocalcin and Bone Sialoprotein Mediating Osteomimicry of Prostate Cancer Cells: Role of cAMP-Dependent Protein Kinase A Signaling Pathway
Huang, W., Xie, Z., Konaka, H., Sodek, J., Zhau, H. E., & Chung, L. W. K. (2005) · Cancer Research · doi:10.1158/0008-5472.can-04-3448 · Cited by 137 · see citing works
REGULATION OF BMP-INDUCED TRANSCRIPTION IN CULTURED HUMAN BONE MARROW STROMAL CELLS
Diefenderfer, D. L., Osyczka, A. M., Garino, J. P., & Leboy, P. S. (2003) · Journal of Bone and Joint Surgery · doi:10.2106/00004623-200300003-00005 · Cited by 121 · see citing works
Gene expression profiling of glucocorticoid-inhibited osteoblasts
Leclerc, N., Luppen, C., Ho, V., Nagpal, S., Hacia, J., Smith, E., & Frenkel, B. (2004) · Journal of Molecular Endocrinology · doi:10.1677/jme.0.0330175 · Cited by 116 · see citing works
“Inhibition of mineralized extracellular matrix formation by GCs was recapitulated in vitro using the MC3T3-E1 cell line and occurred only when GC treatment commenced prior to the seventh day of culture (Lian et al. 1997).”
BackgroundSelf-citation
Glucocorticoids Inhibit Developmental Stage-specific Osteoblast Cell Cycle
Smith, E., Redman, R. A., Logg, C. R., Coetzee, G. A., Kasahara, N., & Frenkel, B. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m001758200 · Cited by 113 · see citing works
Self-citation
Bone Morphogenetic Protein-2 Restores Mineralization in Glucocorticoid-Inhibited MC3T3-E1 Osteoblast Cultures
Luppen, C. A., Smith, E., Spevak, L., Boskey, A. L., & Frenkel, B. (2003) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.2003.18.7.1186 · Cited by 108 · see citing works
“In this study, we used MC3T3-E1 cells, in which mineralized matrix formation is strongly inhibited by GC.(5,57) It should be noted that in MC3T3-E1 cells, like in rat calvarial osteoblasts,(58) GCs do not promote, but in fact inhibit, apoptosis (data not shown).”
MethodSelf-citation
Inductive Effects of Dexamethasone on the Gene Expression of Cbfa1, Osterix and Bone Matrix Proteins During Differentiation of Cultured Primary Rat Osteoblasts
Igarashi, M., Kamiya, N., Hasegawa, M., Kasuya, T., Takahashi, T., & Takagi, M. (2004) · Journal of Molecular Histology · doi:10.1023/b:hijo.0000020883.33256.fe · Cited by 108 · see citing works
“…et al. 1998, Ogston et al. 2002) and the present studies are presumably related to the effect of glucocorticoids, which depends on the degree of cellular differentiation and the donor species (Chen et al. 1983a,b, Lian et al. 1997) as well as the dose and duration of exposure (Jonsson et al. 1997).”
BackgroundResultInfluential
Composite PLA/PEG/nHA/Dexamethasone Scaffold Prepared by 3D Printing for Bone Regeneration
Li, X., Wang, Y., Wang, Z., Qi, Y., Li, L., Zhang, P., Chen, X., & Huang, Y. (2018) · Macromolecular Bioscience · doi:10.1002/mabi.201800068 · Cited by 101 · see citing works
Gene expression analysis in human osteoblasts exposed to dexamethasone identifies altered developmental pathways as putative drivers of osteoporosis
Hurson, C. J., Butler, J. S., Keating, D., Murray, D. W., Sadlier, D. M., O’Byrne, J., & Doran, P. (2007) · BMC Musculoskeletal Disorders · doi:10.1186/1471-2474-8-12 · Cited by 100 · see citing works
“They inhibit osteoblastogenesis and osteoclastogenesis and reduce osteoblast lifespan of [9-11].”
Differentiation stage alters matrix control of stem cells
Hsiong, S. X., Carampin, P., Kong, H., Lee, K. Y., & Mooney, D. J. (2007) · Journal of Biomedical Materials Research Part A · doi:10.1002/jbm.a.31521 · Cited by 97 · see citing works
Microcalcifications in breast cancer: Lessons from physiological mineralization
Cox, R. F., & Morgan, M. P. (2013) · Bone · doi:10.1016/j.bone.2013.01.013 · Cited by 96 · see citing works
“It has been suggested that the effect of dexamethasone is species-specific, as in themouse pre-osteoblast MC3T3-E1 cell line addition of dexamethasone decreases mineralization compared to the osteogenic cocktail alone [36].”
Result
Vitamin D endocrinology of bone mineralization
van Driel, M., & van Leeuwen, J. P. T. M. (2017) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2017.06.008 · Cited by 95 · see citing works
Cyclic Arginine-Glycine-Aspartate Peptides Enhance Three-Dimensional Stem Cell Osteogenic Differentiation
Hsiong, S. X., Boontheekul, T., Huebsch, N., & Mooney, D. J. (2008) · Tissue Engineering Part A · doi:10.1089/ten.tea.2007.0411 · Cited by 94 · see citing works
Activation of Osteocalcin Transcription Involves Interaction of Protein Kinase A- and Protein Kinase C-dependent Pathways
Boguslawski, G., Hale, L. V., Yu, X., Miles, R. R., Onyia, J. E., Santerre, R. F., & Chandrasekhar, S. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.275.2.999 · Cited by 94 · see citing works
Vitamin D endocrine system and osteoblasts.
van Driel, M., & van Leeuwen, J. (2014) · BoneKEy Reports · doi:10.1038/bonekey.2013.227 · Cited by 81 · see citing works
Expression of non-neuronal cholinergic system in osteoblast-like cells and its involvement in osteogenesis
En-Nosse, M., Hartmann, S., Trinkaus, K., Alt, V., Stigler, B., Heiß, C., Kilián, O., Schnettler, R., & Lips, K. S. (2009) · Cell and Tissue Research · doi:10.1007/s00441-009-0871-1 · Cited by 88 · see citing works
“…using RT-PCR in native MC3T3-E1 and MC3T3-E1 cells incubated with DMEM containing FCS, dexamethasone, ascorbic acid-2 phosphate, and β-glycerolphosphate, a formulation used for osteogenetic differentiation of cells from human reaming debris into osteoblasts (Wenisch et al. 2005; Lian et al. 1997).”
BackgroundMethod
Sustained In Vitro Expansion of Bone Progenitors Is Cell Density Dependent
Purpura, K. A., Aubin, J. E., & Zandstra, P. W. (2004) · Stem Cells · doi:10.1634/stemcells.22-1-39 · Cited by 85 · see citing works
Regulated Expression of the Bone-Specific Osteocalcin Gene by Vitamins and Hormones
Lian, J. B., Stein, G. S., Stein, J. L., & van Wijnen, A. J. (1998) · Vitamins and hormones · doi:10.1016/s0083-6729(08)60941-3 · Cited by 84 · see citing works
Self-citation
Vitamin D Receptor Interactions with the Rat Parathyroid Hormone Gene: Synergistic Effects Between Two Negative Vitamin D Response Elements
Russell, J., Ashok, S., & Koszewski, N. J. (1999) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.1999.14.11.1828 · Cited by 83 · see citing works
Cortisol regulates the expression of Notch in osteoblasts
Pereira, R. M. R., Delany, A. M., Durant, D., & CANALIS, E. M. (2002) · Journal of Cellular Biochemistry · doi:10.1002/jcb.10125 · Cited by 80 · see citing works
Vitamin D and Bone: A Story of Endocrine and Auto/Paracrine Action in Osteoblasts
van Driel, M., & van Leeuwen, J. P. T. M. (2023) · Nutrients · doi:10.3390/nu15030480 · Cited by 82 · see citing works
Greek Plant Extracts Exhibit Selective Estrogen Receptor Modulator (SERM)-like Properties
Kassi, E. N., Papoutsi, Z., Fokialakis, N., Messari, I., Mitakou, S., & Moutsatsou, P. (2004) · Journal of Agricultural and Food Chemistry · doi:10.1021/jf0400765 · Cited by 79 · see citing works
Osteomimicry of Mammary Adenocarcinoma Cells In Vitro; Increased Expression of Bone Matrix Proteins and Proliferation within a 3D Collagen Environment
Cox, R. F., Jenkinson, A., Pohl, K., O’Brien, F. J., & Morgan, M. P. (2012) · PLoS ONE · doi:10.1371/journal.pone.0041679 · Cited by 73 · see citing works
1,25-(OH)2D3Down-Regulates Expression ofPhex, a Marker of the Mature Osteoblast1
Ecarot, B., & Desbarats, M. (1999) · Endocrinology · doi:10.1210/endo.140.3.6593 · Cited by 71 · see citing works
Mapping calcium phosphate activated gene networks as a strategy for targeted osteoinduction of human progenitors
Eyckmans, J., Roberts, S. J., Bolander, J., Schrooten, J., Chen, C. S., & Luyten, F. P. (2013) · Biomaterials · doi:10.1016/j.biomaterials.2013.03.011 · Cited by 68 · see citing works
Human and Murine Osteocalcin Gene Expression: Conserved Tissue Restricted Expression and Divergent Responses to 1,25-Dihydroxyvitamin D3 in Vivo
Sims, N. A., White, C., Sunn, K. L., Thomas, G. P., Drummond, M. L., Morrison, N. A., Eisman, J. A., & Gardiner, E. M. (1997) · Molecular Endocrinology · doi:10.1210/mend.11.11.0008 · Cited by 68 · see citing works
“Supporting this concept, recent studies have verified such a species-related difference, showing the mouse osteocalcin gene to be down-regulated rather than induced by 1,25-(OH)2D3 in vivo and in vitro (38, 39).”
The Response of Human Mesenchymal Stem Cells to Osteogenic Signals and its Impact on Bone Tissue Engineering
Siddappa, R., Fernandes, H., Liu, J., van Blitterswijk, C., & de Boer, J. (2007) · Current Stem Cell Research & Therapy · doi:10.2174/157488807781696267 · Cited by 65 · see citing works
The role of sirtuin 1 in osteoblastic differentiation in human periodontal ligament cells
Lee, Y. ‐., Shin, S., Shin, K. ‐., Lee, Y., Park, B., & Kim, E. ‐. (2011) · Journal of Periodontal Research · doi:10.1111/j.1600-0765.2011.01394.x · Cited by 64 · see citing works
Osteoprogenitor cells in cell populations derived from mouse and rat calvaria differ in their response to corticosterone, cortisol, and cortisone1
Bellows, C. G., Ciaccia, A., & Heersche, J. N. M. (1998) · Bone · doi:10.1016/s8756-3282(98)00084-2 · Cited by 64 · see citing works
Vitamin D receptor and retinoid X receptor interactions in motion
Bársony, J., & Prüfer, K. (2002) · Vitamins and hormones · doi:10.1016/s0083-6729(02)65071-x · Cited by 63 · see citing works
Osteocalcin Production in Primary Osteoblast Cultures Derived from Normal and Hyp Mice
Carpenter, T. O., Moltz, K. C., Ellis, B. K., Andreoli, M., McCarthy, T. L., Bryan, D., & Gundberg, C. M. (1998) · Endocrinology · doi:10.1210/endo.139.1.5677 · Cited by 62 · see citing works
Both direct and collagen-mediated signals are required for active vitamin D3-elicited differentiation of human osteoblastic cells: Roles of osterix, an osteoblast-related transcription factor
Maehata, Y., Takamizawa, S., Ozawa, S., Kato, Y., Sato, S., Kubota, E., & Hata, R. (2005) · Matrix Biology · doi:10.1016/j.matbio.2005.09.001 · Cited by 62 · see citing works
Dexamethasone modulates osteogenesis and adipogenesis with regulation of osterix expression in rat calvaria‐derived cells
Mikami, Y., Lee, M., Irie, S., & Honda, M. J. (2010) · Journal of Cellular Physiology · doi:10.1002/jcp.22392 · Cited by 60 · see citing works
“Dexamethasone (Dex) is a synthetic glucocorticoid (GC) that is frequently used in the treatment of severe inflammatory diseases (Lian et al., 1997).”
Background
The local production of 1,25(OH)2D3 promotes osteoblast and osteocyte maturation
Turner, A. G., Hanrath, M. A., Morris, H. A., Atkins, G. J., & Anderson, P. H. (2014) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2013.10.003 · Cited by 57 · see citing works
Conditionally Immortalized Murine Bone Marrow Stromal Cells Mediate Parathyroid Hormone-Dependent Osteoclastogenesisin Vitro1
Liu, B.-Y., Guo, J., Lanske, B., Pajevic, P. D., Kronenberg, H. M., & Bringhurst, F. R. (1998) · Endocrinology · doi:10.1210/endo.139.4.5895 · Cited by 59 · see citing works
Brief Bone Morphogenetic Protein 2 Treatment of Glucocorticoid-inhibited MC3T3-E1 Osteoblasts Rescues Commitment-associated Cell Cycle and Mineralization without Alteration of Runx2
Luppen, C. A., Leclerc, N., Noh, T., Barski, A., Khokhar, A., Boskey, A. L., Smith, E., & Frenkel, B. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m306730200 · Cited by 58 · see citing works
Self-citation
Inductive effects of dexamethasone on the mineralization and the osteoblastic gene expressions in mature osteoblast-like ROS17/2.8 cells
Mikami, Y., Omoteyama, K., Kato, S., & Takagi, M. (2007) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2007.07.192 · Cited by 57 · see citing works
Substance P Enhances the Inhibition of Osteoblastic Cell Differentiation Induced by Lipopolysaccharide From Porphyromonas gingivalis
Azuma, H., Kido, J., Ikedo, D., Kataoka, M., & Nagata, T. (2004) · Journal of Periodontology · doi:10.1902/jop.2004.75.7.974 · Cited by 57 · see citing works
1,25-Dihydroxyvitamin D and Klotho
Haussler, M. R., Whitfield, G. K., Haussler, C. A., Sabir, M. S., Khan, Z., Sandoval, R., & Jurutka, P. W. (2016) · Vitamins and hormones · doi:10.1016/bs.vh.2015.11.005 · Cited by 54 · see citing works
Glucocorticoids inhibit osteocalcin transcription in osteoblasts by suppressing Egr2/Krox20‐binding enhancer
Leclerc, N., Noh, T., Khokhar, A., Smith, E., & Frenkel, B. (2005) · Arthritis & Rheumatism · doi:10.1002/art.20872 · Cited by 54 · see citing works
Self-citation
24,25-Dihydroxyvitamin D3 and bone metabolism
van Leeuwen, J. P. T. M., van den Bemd, G.-J. C. M., van Driel, M., Buurman, C. J., & Pols, H. A. P. (2001) · Steroids · doi:10.1016/s0039-128x(00)00155-0 · Cited by 53 · see citing works
Parathyroid Hormone Induction of the Osteocalcin Gene
Jiang, D., Franceschi, R. T., Boules, H., & Xiao, G. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m311547200 · Cited by 52 · see citing works
Glucocorticoid-induced osteoporosis in the rat is prevented by the tyrosine phosphatase inhibitor, sodium orthovanadate
Hulley, P. A., Conradie, M., Langeveldt, C., & Hough, F. S. (2002) · Bone · doi:10.1016/s8756-3282(02)00807-4 · Cited by 52 · see citing works
Quantitative proteomic analysis of dexamethasone-induced effects on osteoblast differentiation, proliferation, and apoptosis in MC3T3-E1 cells using SILAC
Hong, D., Chen, H.-X., Yu, H., Wang, C., Deng, H., Lian, Q., & Ge, R. (2010) · Osteoporosis International · doi:10.1007/s00198-010-1434-8 · Cited by 51 · see citing works
“In accordance with the previous data [13–16], we demonstrated that a high dose of DEX inhibited osteoblast differentiation and cell proliferation but promoted apoptosis in MC3T3-E1 cells on day 7.”
Mouse embryo‐derived NIH3T3 fibroblasts adopt an osteoblast‐like phenotype when treated with 1α,25‐dihydroxyvitamin D3 and dexamethasone in vitro
Shui, C., & Scutt, A. M. (2002) · Journal of Cellular Physiology · doi:10.1002/jcp.10157 · Cited by 48 · see citing works
“Unfortunately, the effects of glucocorticoids on VDR levels are not clear, there have been reports of glucocorticoids apparently increasing (Maenpaa et al., 1991), decreasing (Godschalk et al., 1992), or have no effect (Mahonen and Maenpaa, 1994) on VDR levels in osteoblastic cells.”
Background
Enhancement of osteogenic gene expression for the differentiation of human periosteal derived cells
Roberts, S. J., Chen, Y., Moesen, M., Schrooten, J., & Luyten, F. P. (2011) · Stem Cell Research · doi:10.1016/j.scr.2011.04.003 · Cited by 46 · see citing works
“For example Dex has been shown to block osteogenic differentiation of murine osteoprogenitor cells with VitD3 shown to down regulate osteocalcin (OCN) within the same cell type (Lian et al., 1997).”
Background
Calcitriol Upregulates Expression and Activity of the 1b Isoform of the Plasma Membrane Calcium Pump in Immortalized Distal Kidney Tubular Cells
Glendenning, P., Ratajczak, T., Dick, I. M., & Prince, R. L. (2000) · Archives of Biochemistry and Biophysics · doi:10.1006/abbi.2000.1908 · Cited by 46 · see citing works
Clinical and Basic Aspects of Glucocorticoid Action in Bone
Kream, B. E., Graves, L., & Lukert, B. P. (2008) · Elsevier eBooks · doi:10.1016/b978-0-12-373884-4.00061-6 · Cited by 46 · see citing works
Involvement of SMRT Corepressor in Transcriptional Repression by the Vitamin D Receptor
‍Kim, D. Y., Son, Y. L., & Lee, Y. C. (2008) · Molecular Endocrinology · doi:10.1210/me.2008-0426 · Cited by 44 · see citing works
“tamin D (D3) (13, 14) and glucocorticoids (15, 16), and a num-”
Periostin and transforming growth factor β‐induced protein ( TGF β I p) are both expressed by osteoblasts and osteoclasts
Merle, B., Bouet, G., Rousseau, J., Bertholon, C., & Garnero, P. (2013) · Cell Biology International · doi:10.1002/cbin.10219 · Cited by 43 · see citing works
“Indeed, 1.25 (OH)2D3 did not influence differentiation of mouse osteoblastic cells assessed by the expression of ALP, osteocalcin and collagen I mRNA, but stimulated the differentiation of human osteoblasts (Lian et al., 1997; Song et al., 2011).”
BackgroundInfluential
Regulation of Osteocalcin Production and Bone Resorption by 1,25-Dihydroxyvitamin D3 in Mouse Long Bones: Interaction with the Bone-Derived Growth Factors TGF-β and IGF-I
Staal, A., Geertsma-Kleinekoort, W. M. C., van den Bemd, G. J. C. M., Buurman, C. J., Birkenhäger, J. C., Pols, H. A. P., & van Leeuwen, J. P. T. M. (1998) · Journal of Bone and Mineral Research · doi:10.1359/jbmr.1998.13.1.36 · Cited by 43 · see citing works
“(33,34) Previously, it was shown that the hypophosphatemic Hyp mice have increased serum osteocalcin levels, which are reduced by 1,25(OH)2D3 treatment.”
Background
BMP-2 vs. BMP-4 expression and activity in glucocorticoid-arrested MC3T3-E1 osteoblasts: Smad signaling, not alkaline phosphatase activity, predicts rescue of mineralization
Luppen, C. A., Luppen, C. A., Chandler, R. L., Noh, T., Mortlock, D. P., & Frenkel, B. (2008) · Growth Factors · doi:10.1080/08977190802277880 · Cited by 43 · see citing works
“2003a) and mineralization in MC3T3-E1 osteoblast cultures (Lian et al. 1997; Luppen et al. 2003b; Smith et al. 1999), and that rhBMP-2 rescues mineralization in this model system (Luppen et al.”
BackgroundSelf-citation
AP-1 and Vitamin D Receptor (VDR) Signaling Pathways Converge at the Rat Osteocalcin VDR Element: Requirement for the Internal Activating Protein-1 Site for Vitamin D-Mediated Trans-Activation**This work was supported by NIH Grants AR-45689, AR-39588, and DE-12528. The contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH.
Aslam, F., McCabe, L. R., Frenkel, B., van Wijnen, A. J., Stein, G. S., Lian, J. B., & Stein, J. L. (1999) · Endocrinology · doi:10.1210/endo.140.1.6429 · Cited by 43 · see citing works
Self-citation
The expression of matrix metalloproteinase‐13 and osteocalcin in mouse osteoblasts is related to osteoblastic differentiation and is modulated by 1,25‐dihydroxyvitamin D3 and thyroid hormones
Fratzl‐Zelman, N., Glantschnig, H., Rumpler, M., Nader, A., Ellinger, A., & Varga, F. (2003) · Cell Biology International · doi:10.1016/s1065-6995(03)00037-4 · Cited by 42 · see citing works
“Consistent with earlier reports (Lian et al., 1997; Zhang et al., 1997), 1,25-(OH)2D3 did not stimulate Osc expression in mice (Fig.”
BackgroundResultInfluential
Nuclear Vitamin D Receptor: Structure-Function, Molecular Control of Gene Transcription, and Novel Bioactions
Whitfield, G., Jurutka, P., Haussler, C., Hsieh, J.-C., Barthel, T., Jacobs, E. T., Dominguez, C. E., Thatcher, M. L., & Haussler, M. (2005) · Elsevier eBooks · doi:10.1016/b978-012252687-9/50016-4 · Cited by 48 · see citing works
Effect of dexamethasone as osteogenic supplementation in in vitro osteogenic differentiation of stem cells from human exfoliated deciduous teeth
Sordi, M. B., Curtarelli, R. B., Silva, I. T., Fongaro, G., Benfatti, C. A. M., Magini, R. D. S., & da Cruz, A. C. C. (2021) · Journal of Materials Science Materials in Medicine · doi:10.1007/s10856-020-06475-6 · Cited by 40 · see citing works
“[14] that found inhibition of osteoblastic differentiation of MC3T3E1 by the chronic use of DEX through the downregulation of osteocalcin gene expression.”
Background
Sclerostin activity plays a key role in the negative effect of glucocorticoid signaling on osteoblast function in mice
Beier, E. E., Sheu, T., Resseguie, E. A., Takahata, M., Awad, H. A., Cory‐Slechta, D. A., & Puzas, J. E. (2017) · Bone Research · doi:10.1038/boneres.2017.13 · Cited by 40 · see citing works
Physiological concentrations of genistein stimulate the proliferation and protect against free radical-induced oxidative damage of MC3T3-E1 osteoblast-like cells
Lee, Y.-S., Chen, X., & Anderson, J. J. B. (2001) · Nutrition Research · doi:10.1016/s0271-5317(01)00340-2 · Cited by 39 · see citing works
Contributions of nuclear architecture and chromatin to vitamin D-dependent transcriptional control of the rat osteocalcin gene
Lian, J. B., Stein, J. L., Stein, G. S., Montecino, M. A., van Wijnen, A. J., Javed, A., & Gutiérrez, S. (2001) · Steroids · doi:10.1016/s0039-128x(00)00160-4 · Cited by 39 · see citing works
Self-citation
Glucocorticoid receptor and Histone deacetylase 6 mediate the differential effect of dexamethasone during osteogenesis of mesenchymal stromal cells (MSCs)
Rimando, M. G., Wu, H.-H., Liu, Y.-A., Lee, C., Kuo, S.-W., Lo, Y.-P., Tseng, K., Liu, Y., & Lee, O. K. (2016) · Scientific Reports · doi:10.1038/srep37371 · Cited by 38 · see citing works
Aluminum Accelerates Osteoblastic Differentiation But is Cytotoxic in Long-Term Rat Calvaria Cell Cultures
Bellows, C. G., Heersche, J. N. M., & Aubin, J. E. (1999) · Calcified Tissue International · doi:10.1007/s002239900658 · Cited by 37 · see citing works
“One possibility is that the differences reflect species differences between the rat and mouse since these two species also differ greatly in their response to glucocorticoid hormones [33–35].”
Background
Dioxin-induced up-regulation of the active form of vitamin D is the main cause for its inhibitory action on osteoblast activities, leading to developmental bone toxicity☆
Nishimura, N., Nishimura, H., Ito, T., Miyata, C., Izumi, K., Fujimaki, H., & Matsumura, F. (2009) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2009.01.025 · Cited by 37 · see citing works
Development of a Three-Dimensional Bone-Like Construct in a Soft Self-Assembling Peptide Matrix
Marí‐Buyé, N., Luque, T., Navajas, D., & Semino, C. E. (2012) · Tissue Engineering Part A · doi:10.1089/ten.tea.2012.0077 · Cited by 35 · see citing works
Full-mouth rehabilitation using dental implants in a patient with scleroderma.
Zigdon, H., Gutmacher, Z., Teich, S., & Levin, L. (2011) · PubMed · Cited by 30 · see citing works
Characterization of a novel hexameric repeat DNA sequence in the promoter of the immediate early gene, IEX-1, that mediates 1α,25-dihydroxyvitamin D3-associated IEX-1 gene repression
Im, H., Craig, T. A., Pittelkow, M. R., & Kumar, R. (2002) · Oncogene · doi:10.1038/sj.onc.1205450 · Cited by 27 · see citing works
“The rat and human osteocalcin VDREs mediate positive regulation, but when two bases are substituted in the 5' steroid half element, repression of the promoter activity was observed upon treatment with vitamin D3 (Lian et al., 1997).”
Background
Nuclear Vitamin D Receptor: Natural Ligands, Molecular Structure–Function, and Transcriptional Control of Vital Genes
Haussler, M. R., Whitfield, G. K., Haussler, C. A., Hsieh, J., & Jurutka, P. W. (2011) · Elsevier eBooks · doi:10.1016/b978-0-12-381978-9.10008-3 · Cited by 26 · see citing works
Inhibition of the tissue reaction to a biodegradable biomaterial by monoclonal antibodies to IFN-?
Khouw, I. M. S. L., van Wachem, P. B., de Leij, L. F. M. H., & van Luyn, M. J. A. (1998) · Journal of Biomedical Materials Research · doi:10.1002/(sici)1097-4636(199808)41:2 · Cited by 53 · see citing works
Retinoic acid induces two osteocalcin isoforms and inhibits markers of osteoclast activity in Atlantic cod (Gadus morhua) ex vivo cultured craniofacial tissues
Lie, K. K., & Moren, M. (2011) · Comparative Biochemistry and Physiology Part A Molecular & Integrative Physiology · doi:10.1016/j.cbpa.2011.10.023 · Cited by 25 · see citing works
Hormonal Regulation of the Osteoblastic Phenotype Expression in Neonatal Murine Calvarial Cells
Chen, T. L., & Fry, D. (1999) · Calcified Tissue International · doi:10.1007/s002239900624 · Cited by 25 · see citing works
Species-Divergent Regulation of Human and Mouse Osteocalcin Genes by Calciotropic Hormones
Thomas, G. P., Bourne, A., Eisman, J. A., & Gardiner, E. M. (2000) · Experimental Cell Research · doi:10.1006/excr.2000.4912 · Cited by 24 · see citing works
Secreted factors from adipose tissue increase adipogenic differentiation of mesenchymal stem cells
Wu, L., Wang, T., Ge, Y., Cai, X., Wang, J., & Lin, Y. (2012) · Cell Proliferation · doi:10.1111/j.1365-2184.2012.00823.x · Cited by 23 · see citing works
The dosage effects of dexamethasone on osteogenic activity andbiocompatibility of poly(lactic-co-glycolic acid)/hydroxyapatite nanofibers
Li, C., Wang, B., Liu, X., Pan, Z., Liu, C., Ma, H., Liu, X., Liu, L., & Jiang, C. (2019) · Artificial Cells Nanomedicine and Biotechnology · doi:10.1080/21691401.2019.1609007 · Cited by 22 · see citing works
“Liano and co-workers indicated that exposure of MC3T3-E1 cells to Dex, initiated during the proliferation period, blocked osteoblast differentiation, had a negative effect on ALP activity, which is consistent with our results [36].”
Result
Fluorescence activated cell sorting reveals heterogeneous and cell non‐autonomous osteoprogenitor differentiation in fetal rat calvaria cell populations
Purpura, K. A., Zandstra, P. W., & Aubin, J. E. (2003) · Journal of Cellular Biochemistry · doi:10.1002/jcb.10596 · Cited by 20 · see citing works
“Immunolabeling of RC cultures was done as described previously [Liu et al., 1994].”
Method
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Self-citation
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Self-citation
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
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Self-citation
The expression of matrix metalloproteinase‐13 and osteocalcin in mouse osteoblasts is related to osteoblastic differentiation and is modulated by 1,25‐dihydroxyvitamin D3 and thyroid hormones
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Authors: Lian, J. B., Shalhoub, V., Aslam, F., Frenkel, B., Green, J., Hamrah, M., Stein, G. S., & Stein, J. L.
Affiliations: University of Massachusetts Chan Medical School (US)
ORCID: Lian, Jane B.
Shalhoub, Victoria
Frenkel, Baruch
Stein, Gary S.
Stein, Janet L.
Venue: Endocrinology
Publisher: The Endocrine Society
Published: 1997-05-01
Volume: 138
Issue: 5
Pages: 2117-2127
ISSN: 0013-7227 (ISSN-L)
1945-7170
DOI: 10.1210/endo.138.5.5117
OpenAlex: W2169357450
Cited by: 154
References: 56
Citations by year: 2023: 3 · 2021: 3 · 2020: 2 · 2019: 1 · 2018: 3 · 2017: 3 · 2016: 4 · 2015: 3 · 2014: 2 · 2013: 6 · 2012: 10
FWCI: 3.90
Type: journal article
Language: en
Open access: closed
Locations: Endocrinology (publishedVersion)
PubMed (publishedVersion)
The Journal of the American Medical Association (JAMA) Network (American Medical Association) (submittedVersion)
Funders: National Institutes of Health (5r01ar033920-12, 5r01dk046721-03)
National Institute of Diabetes and Digestive and Kidney Diseases (DK-46721)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (AR33920)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
Health Sciences › Medicine › Pathology and Forensic Medicine › Vitamin D Research Studies
Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
Keywords: glucocorticoids, 1,25-dihydroxyvitamin D3, dexamethasone, osteogenic differentiation, MC3T3-E1 cells, osteocalcin gene expression, vitamin D response element, osteoblast maturation, bone mineralization, glucocorticoid receptor, 1,25-dihydroxyvitamin D3 receptor, osteopontin, collagen, histone H2B
MeSH terms: Animals, Base Sequence, Calcitriol, Cell Differentiation, Cell Line, Dexamethasone, Glucocorticoids, Histones, Osteoblasts, Promoter Regions, Genetic, RNA, Messenger, Time Factors, Transfection, Osteocalcin, Gene Expression, Mice

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Species-specific glucocorticoid and 1,25-dihydroxyvitamin D responsiveness in mouse MC3T3–E1 osteoblasts: dexamethasone inhibits osteoblast differentiation and vitamin D down-regulates osteocalcin gene expression.

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