Potential for Drug Repositioning of Midazolam for Dentin Regeneration.

Animals Bone Morphogenetic Protein 2 / pharmacology Cell Line Dentin / drug effects Drug Repositioning Midazolam / pharmacology Odontoblasts Regeneration Swine Transforming Growth Factor beta1 / pharmacology
cell dentin drug repositioning hydroxyapatite nanoparticle nanorod

Journal

International journal of molecular sciences
ISSN: 1422-0067
Titre abrégé: Int J Mol Sci
Pays: Switzerland
ID NLM: 101092791

Informations de publication

Date de publication:
04 Feb 2019
Historique:
received: 13 12 2018
revised: 24 01 2019
accepted: 31 01 2019
entrez: 6 2 2019
pubmed: 6 2 2019
medline: 25 6 2019
Statut: epublish

Résumé

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.

Identifiants

DOI: 10.3390/ijms20030670 PMID: 30720745 PMC: PMC6387224
pubmed: 30720745
pii: ijms20030670
doi: 10.3390/ijms20030670
pmc: PMC6387224
pii:
doi:

Substances chimiques

Bone Morphogenetic Protein 2 0
Transforming Growth Factor beta1 0
Midazolam R60L0SM5BC

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Subventions

Organisme : JSPS KAKENHI Grant-in-Aid for Scientific Research
ID : C26462982, 16K04954, 17K11975, 18K09630
Organisme : MEXT-Supported Program for the Strategic Research Foundation at Private Universities
ID : S1511018

Déclaration de conflit d'intérêts

The authors declare no conflict of interest.

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Auteurs

Takeo Karakida (T)

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.

Kazuo Onuma (K)

National Institute of Advanced Industrial Science & Technology, Central 6, 1-1-1 Higashi, Tsukuba,Ibaraki 305-8566, Japan. k.onuma@aist.go.jp.

Mari M Saito (MM)

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.
ORCID: 0000-0003-4058-7371

Ryuji Yamamoto (R)

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.

Toshie Chiba (T)

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.

Risako Chiba (R)

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.

Yukihiko Hidaka (Y)

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.

Keiko Fujii-Abe (K)

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.

Hiroshi Kawahara (H)

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.
ORCID: 0000-0002-4423-3004

Yasuo Yamakoshi (Y)

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.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Potential for Drug Repositioning of Midazolam...
questionsmedicales.fr › Facteurs biologiques › Protéines et peptides de signalisation intercellulaire › Protéines de la superfamille du TGF bêta › Protéines morphogénétiques osseuses › Protéine morphogénétique osseuse de type 2 › Potential for Drug Repositioning of Midazolam...
questionsmedicales.fr › Cellules › Cellules cultivées › Lignée cellulaire › Potential for Drug Repositioning of Midazolam...
questionsmedicales.fr › Système stomatognathique › Bouche › Denture › Composants dentaires › Dentine › Potential for Drug Repositioning of Midazolam...
questionsmedicales.fr › Techniques d'investigation › Développement de médicament › Repositionnement des médicaments › Potential for Drug Repositioning of Midazolam...
questionsmedicales.fr › Composés hétérocycliques › Composés hétérocycliques à cycles fusionnés › Composés hétérobicycliques › Benzazépines › Benzodiazépines › Midazolam › Potential for Drug Repositioning of Midazolam...
questionsmedicales.fr › Cellules › Cellules du tissu conjonctif › Odontoblastes › Potential for Drug Repositioning of Midazolam...
questionsmedicales.fr › Phénomènes biologiques › Régénération › Potential for Drug Repositioning of Midazolam...
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