Osteogenic Differentiation of Stem Cells Alters Vitamin D Receptor Expression

Overview

Journal Stem Cells Dev

Date 2011 Nov 1

PMID 22034957

Citations 14

Authors

Rene Olivares-Navarrete

Ken Sutha

Sharon L Hyzy

Daphne L Hutton

Zvi Schwartz

Todd McDevitt

Barbara D Boyan

Affiliations

Soon will be listed here.

Abstract

Pluripotent and multipotent stem cells adopt an osteoblastic phenotype when cultured in environments that enhance their osteogenic potential. Embryonic stem cells differentiated as embryoid bodies (EBs) in osteogenic medium containing β-glycerophosphate exhibit increased expression of bone markers, indicating that cells are osteoblastic. Interestingly, 1α,25-dihydroxyvitaminD3 (1,25D) enhances the osteogenic phenotype not just in EBs but also in multipotent adult mesenchymal stem cells (MSCs). 1,25D acts on osteoblasts via classical vitamin D receptors (VDR) and via a membrane 1,25D-binding protein [protein disulfide isomerase family A, member 3 (PDIA3)], which activates protein kinase C-signaling. The aims of this study were to determine whether these receptors are regulated during osteogenic differentiation of stem cells and if stem cells and differentiated progeny are responsive to 1,25D. mRNA and protein levels for VDR, PDIA3, and osteoblast-associated proteins were measured in undifferentiated cells and in cells treated with osteogenic medium. Mouse EBs expressed both VDR and PDIA3, but VDR increased as cells underwent osteogenic differentiation. Human MSCs expressed Pdia3 at constant levels throughout differentiation, but VDR increased in cells treated with osteogenic medium. These results suggest that both 1,25D signaling mechanisms are important, with PDIA3 playing a greater role during early events and VDR playing a greater role in later stages of differentiation. Understanding these coordinated events provide a powerful tool to control pluripotent and multipotent stem cell differentiation through induction medium.

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References

Martin J, Dean D, Cochran D, Simpson J, Boyan B, Schwartz Z . Proliferation, differentiation, and protein synthesis of human osteoblast-like cells (MG63) cultured on previously used titanium surfaces. Clin Oral Implants Res. 1996; 7(1):27-37. DOI: 10.1034/j.1600-0501.1996.070104.x. View

Wang Y, Chen J, Lee C, Nizkorodov A, Riemenschneider K, Martin D . Disruption of Pdia3 gene results in bone abnormality and affects 1alpha,25-dihydroxy-vitamin D3-induced rapid activation of PKC. J Steroid Biochem Mol Biol. 2010; 121(1-2):257-60. DOI: 10.1016/j.jsbmb.2010.05.004. View

Kurosawa H . Methods for inducing embryoid body formation: in vitro differentiation system of embryonic stem cells. J Biosci Bioeng. 2007; 103(5):389-98. DOI: 10.1263/jbb.103.389. View

Coucouvanis E, Martin G . Signals for death and survival: a two-step mechanism for cavitation in the vertebrate embryo. Cell. 1995; 83(2):279-87. DOI: 10.1016/0092-8674(95)90169-8. View

Khanal R, Nemere I . The ERp57/GRp58/1,25D3-MARRS receptor: multiple functional roles in diverse cell systems. Curr Med Chem. 2007; 14(10):1087-93. DOI: 10.2174/092986707780362871. View

Jurutka P, Bartik L, Whitfield G, Mathern D, Barthel T, Gurevich M . Vitamin D receptor: key roles in bone mineral pathophysiology, molecular mechanism of action, and novel nutritional ligands. J Bone Miner Res. 2008; 22 Suppl 2:V2-10. DOI: 10.1359/jbmr.07s216. View

Carpenedo R, Sargent C, McDevitt T . Rotary suspension culture enhances the efficiency, yield, and homogeneity of embryoid body differentiation. Stem Cells. 2007; 25(9):2224-34. DOI: 10.1634/stemcells.2006-0523. View

Jikko A, Harris S, Chen D, Mendrick D, Damsky C . Collagen integrin receptors regulate early osteoblast differentiation induced by BMP-2. J Bone Miner Res. 1999; 14(7):1075-83. DOI: 10.1359/jbmr.1999.14.7.1075. View

Kong C, Akar F, Li R . Translational potential of human embryonic and induced pluripotent stem cells for myocardial repair: insights from experimental models. Thromb Haemost. 2010; 104(1):30-8. DOI: 10.1160/TH10-03-0189. View

10.

Hopfl G, Gassmann M, Desbaillets I . Differentiating embryonic stem cells into embryoid bodies. Methods Mol Biol. 2004; 254:79-98. DOI: 10.1385/1-59259-741-6:079. View

11.

van Leeuwen J, van Driel M, van den Bemd G, Pols H . Vitamin D control of osteoblast function and bone extracellular matrix mineralization. Crit Rev Eukaryot Gene Expr. 2001; 11(1-3):199-226. View

12.

Conley B, Young J, Trounson A, Mollard R . Derivation, propagation and differentiation of human embryonic stem cells. Int J Biochem Cell Biol. 2004; 36(4):555-67. DOI: 10.1016/j.biocel.2003.07.003. View

13.

Takahashi N, Maeda K, Ishihara A, Uehara S, Kobayashi Y . Regulatory mechanism of osteoclastogenesis by RANKL and Wnt signals. Front Biosci (Landmark Ed). 2011; 16(1):21-30. DOI: 10.2741/3673. View

14.

Bratt-Leal A, Carpenedo R, McDevitt T . Engineering the embryoid body microenvironment to direct embryonic stem cell differentiation. Biotechnol Prog. 2009; 25(1):43-51. PMC: 2693014. DOI: 10.1002/btpr.139. View

15.

Zanello L, Norman A . 1alpha,25(OH)2 vitamin D3 actions on ion channels in osteoblasts. Steroids. 2006; 71(4):291-7. DOI: 10.1016/j.steroids.2005.09.012. View

16.

Chen J, Olivares-Navarrete R, Wang Y, Herman T, Boyan B, Schwartz Z . Protein-disulfide isomerase-associated 3 (Pdia3) mediates the membrane response to 1,25-dihydroxyvitamin D3 in osteoblasts. J Biol Chem. 2010; 285(47):37041-50. PMC: 2978632. DOI: 10.1074/jbc.M110.157115. View

17.

van den Bemd G, Jhamai M, Staal A, van Wijnen A, Lian J, Stein G . A central dinucleotide within vitamin D response elements modulates DNA binding and transactivation by the vitamin D receptor in cellular response to natural and synthetic ligands. J Biol Chem. 2002; 277(17):14539-46. DOI: 10.1074/jbc.M111224200. View

18.

Kraichely D, MacDonald P . Transcriptional activation through the vitamin D receptor in osteoblasts. Front Biosci. 1998; 3:d821-33. DOI: 10.2741/a325. View

19.

Kane N, Meloni M, Spencer H, Craig M, Strehl R, Milligan G . Derivation of endothelial cells from human embryonic stem cells by directed differentiation: analysis of microRNA and angiogenesis in vitro and in vivo. Arterioscler Thromb Vasc Biol. 2010; 30(7):1389-97. DOI: 10.1161/ATVBAHA.110.204800. View

20.

Schwartz Z, Dennis R, Bonewald L, Swain L, Gomez R, Boyan B . Differential regulation of prostaglandin E2 synthesis and phospholipase A2 activity by 1,25-(OH)2D3 in three osteoblast-like cell lines (MC-3T3-E1, ROS 17/2.8, and MG-63). Bone. 1992; 13(1):51-8. DOI: 10.1016/8756-3282(92)90361-y. View