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Originally published In Press as doi:10.1074/jbc.M112223200 on March 19, 2002

J. Biol. Chem., Vol. 277, Issue 22, 19976-19981, May 31, 2002
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Odontoblast Cells Immortalized by Telomerase Produce Mineralized Dentin-like Tissue Both in Vitro and in Vivo*

Jianjun Hao, Karthikeyan Narayanan, Amsaveni Ramachandran, Gen He, Abdullah Almushayt, Carla EvansDagger , and Anne George§

From the Department of Oral Biology and the Dagger  Department of Orthodontics, University of Illinois, Chicago, Illinois 60612

The formation of dentin provides one well accepted paradigm for studying mineralized tissue formation. For the assembly of dentin, several cellular signaling pathways cooperate to provide neural crest-derived mesenchymal cells with positional information. Further, "cross-talk" between signaling pathways from the mesenchymal derived odontoblast cells and the epithelially derived ameloblasts during development is responsible for the formation of functional odontoblasts. These intercellular signals are tightly regulated, both temporally and spatially. When isolated from the developing tooth germ, odontoblasts quickly lose their potential to maintain the odontoblast-specific phenotype. Therefore, generation of an odontoblast cell line would be a valuable reproducible tool for studying the modulatory effects involved in odontoblast differentiation as well as the molecular events involved in mineralized dentin formation. In this study an immortalized odontoblast cell line, which has the required biochemical machinery to produce mineralized tissue in vitro, has been generated. These cells were implanted into animal models to determine their in vivo effects on dentin formation. After implantation, we observed a multistep, programmed cascade of gene expression in the exogenous odontoblasts as the dentin formed de novo. Some of the genes expressed include the dentin matrix proteins 1, 2, and 3, which are extracellular matrix molecules responsible for the ultimate formation of mineralized dentin. The biological response was also examined by histology and radiography and confirmed for mineral deposition by von Kossa staining. Thus, a transformed odontoblast cell line was created with high proliferative capacity that might ultimately be used for the regeneration and repair of dentin in vivo.

* This work was supported by the Department of Orthodontics at University of Illinois at Chicago (to C. E.) and NIDCR, National Institutes of Health Grant DE11657 (to A. G.).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

§ To whom correspondence should be addressed: Dept. of Oral Biology (M/C 690), University of Illinois, Chicago, IL 60612. Tel.: 312-413-0738; Fax: 312-996-6044; E-mail: anneg@uic.edu.

Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
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