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Int J Mol Sci. 2019 Feb 4;20(3). pii: E670. doi: 10.3390/ijms20030670.

Potential for Drug Repositioning of Midazolam for Dentin Regeneration.

Author information

1
Department of Biochemistry and Molecular Biology, School of Dental Medicine, Tsurumi University,2-1-3 Tsurumi, Tsurumi-ku, Yokohama 230-8501, Japan. karakida-t@tsurumi-u.ac.jp.
2
National Institute of Advanced Industrial Science & Technology, Central 6, 1-1-1 Higashi, Tsukuba,Ibaraki 305-8566, Japan. k.onuma@aist.go.jp.
3
Department of Biochemistry and Molecular Biology, School of Dental Medicine, Tsurumi University,2-1-3 Tsurumi, Tsurumi-ku, Yokohama 230-8501, Japan. saito-mari@tsurumi-u.ac.jp.
4
Department of Biochemistry and Molecular Biology, School of Dental Medicine, Tsurumi University,2-1-3 Tsurumi, Tsurumi-ku, Yokohama 230-8501, Japan. yamamoto-rj@tsurumi-u.ac.jp.
5
Research Center of Electron Microscopy, School of Dental Medicine, Tsurumi University, 2-1-3 Tsurumi, Tsurumi-ku, Yokohama 230-8501, Japan. chiba-t@tsurumi-u.ac.jp.
6
Department of Biochemistry and Molecular Biology, School of Dental Medicine, Tsurumi University,2-1-3 Tsurumi, Tsurumi-ku, Yokohama 230-8501, Japan. chiba-r@tsurumi-u.ac.jp.
7
Department of Dental Anesthesiology, School of Dental Medicine, Tsurumi University, 2-1-3 Tsurumi, Tsurumi-ku, Yokohama 230-8501, Japan. 2911002@stu.tsurumi-u.ac.jp.
8
Department of Dental Anesthesiology, School of Dental Medicine, Tsurumi University, 2-1-3 Tsurumi, Tsurumi-ku, Yokohama 230-8501, Japan. fujii-keiko@tsurumi-u.ac.jp.
9
Department of Dental Anesthesiology, School of Dental Medicine, Tsurumi University, 2-1-3 Tsurumi, Tsurumi-ku, Yokohama 230-8501, Japan. kawahara-h@tsurumi-u.ac.jp.
10
Department of Biochemistry and Molecular Biology, School of Dental Medicine, Tsurumi University,2-1-3 Tsurumi, Tsurumi-ku, Yokohama 230-8501, Japan. yamakoshi-y@tsurumi-u.ac.jp.

Abstract

Drug repositioning promises the advantages of reducing costs and expediting approvalschedules. An induction of the anesthetic and sedative drug; midazolam (MDZ), regulatesinhibitory neurotransmitters in the vertebrate nervous system. In this study we show the potentialfor drug repositioning of MDZ for dentin regeneration. A porcine dental pulp-derived cell line(PPU-7) that we established was cultured in MDZ-only, the combination of MDZ with bonemorphogenetic protein 2, and the combination of MDZ with transforming growth factor-beta 1. Thedifferentiation of PPU-7 into odontoblasts was investigated at the cell biological and genetic level.Mineralized nodules formed in PPU-7 were characterized at the protein and crystal engineeringlevels. The MDZ-only treatment enhanced the alkaline phosphatase activity and mRNA levels ofodontoblast differentiation marker genes, and precipitated nodule formation containing a dentinspecificprotein (dentin phosphoprotein). The nodules consisted of randomly orientedhydroxyapatite nanorods and nanoparticles. The morphology, orientation, and chemicalcomposition of the hydroxyapatite crystals were similar to those of hydroxyapatite that hadtransformed from amorphous calcium phosphate nanoparticles, as well as the hydroxyapatite inhuman molar dentin. Our investigation showed that a combination of MDZ and PPU-7 cellspossesses high potential of drug repositioning for dentin regeneration.

KEYWORDS:

cell; dentin; drug repositioning; hydroxyapatite; nanoparticle; nanorod

PMID:
30720745
DOI:
10.3390/ijms20030670
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