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

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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.

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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Calcitriol Upregulates Expression and Activity of the 1b Isoform of the Plasma Membrane Calcium Pump in Immortalized Distal Kidney Tubular Cells
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Involvement of SMRT Corepressor in Transcriptional Repression by the Vitamin D Receptor
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“tamin D (D3) (13, 14) and glucocorticoids (15, 16), and a num-”
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“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
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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
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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.
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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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BackgroundResultInfluential
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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
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Sclerostin activity plays a key role in the negative effect of glucocorticoid signaling on osteoblast function in mice
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Self-citation
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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☆
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Result
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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 › Endocrinology, Diabetes and Metabolism › 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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