Repurposing MDZ as a tool for tissue regeneration in dental cells.

Animals Bone Morphogenetic Proteins / pharmacology Cell Line Drug Repositioning Hydroxyapatites Mice Midazolam Swine
Dental pulp Drug repurposing Hydroxyapatite Midazolam Osteoblast

Journal

Journal of oral biosciences
ISSN: 1880-3865
Titre abrégé: J Oral Biosci
Pays: Netherlands
ID NLM: 101226721

Informations de publication

Date de publication:
03 2022
Historique:
received: 04 10 2021
revised: 20 10 2021
accepted: 22 10 2021
pubmed: 1 11 2021
medline: 3 5 2022
entrez: 31 10 2021
Statut: ppublish

Résumé

Several recent studies have focused on the utility of drug repurposing to expand clinical application of approved therapeutics. Here, we investigate the efficacy of midazolam (MDZ) and cytokines for regenerating calcified tissue, using immortalized porcine dental pulp (PPU7) and mouse skeletal muscle derived myoblast (C2C12) cells, with the goal of repurposing MDZ as a new treatment to facilitate calcified tissue regeneration. We noted that PPU7 and C2C12 cells cultured with various MDZ regimens displayed increased bone morphogenic protein (BMP-2), transforming growth factor beta (TGF-β), and alkaline phosphatase activity. These increases were highest in PPU7 cells cultured with MDZ alone, and in C2C12 cells cultured with MDZ and BMP-2. PPU7 cells cultured under these conditions demonstrated markedly elevated expression of odontoblastic gene markers, indicating their likely differentiation into odontoblasts. Expression levels of osteoblastic gene markers also increased in C2C12 cells, suggesting that MDZ potentiates the effect of BMP-2, inducing osteoblast differentiation in these cells. Newly formed calcified deposits in both PPU7 and C2C12 cells were identified as hydroxyapatite via crystallographic and crystal engineering analyses. MDZ increases ALP activity, inducing expression of specific marker genes for both odontoblasts and osteoblasts while promoting hydroxyapatite production in both PPU7 and C2C12 cells. These responses were cell type specific. MDZ treatment alone could induce these changes in PPU7 cells, but C2C12 cell differentiation required BMP-2 addition.

Sections du résumé

BACKGROUND
Several recent studies have focused on the utility of drug repurposing to expand clinical application of approved therapeutics. Here, we investigate the efficacy of midazolam (MDZ) and cytokines for regenerating calcified tissue, using immortalized porcine dental pulp (PPU7) and mouse skeletal muscle derived myoblast (C2C12) cells, with the goal of repurposing MDZ as a new treatment to facilitate calcified tissue regeneration.
HIGHLIGHTS
We noted that PPU7 and C2C12 cells cultured with various MDZ regimens displayed increased bone morphogenic protein (BMP-2), transforming growth factor beta (TGF-β), and alkaline phosphatase activity. These increases were highest in PPU7 cells cultured with MDZ alone, and in C2C12 cells cultured with MDZ and BMP-2. PPU7 cells cultured under these conditions demonstrated markedly elevated expression of odontoblastic gene markers, indicating their likely differentiation into odontoblasts. Expression levels of osteoblastic gene markers also increased in C2C12 cells, suggesting that MDZ potentiates the effect of BMP-2, inducing osteoblast differentiation in these cells. Newly formed calcified deposits in both PPU7 and C2C12 cells were identified as hydroxyapatite via crystallographic and crystal engineering analyses.
CONCLUSION
MDZ increases ALP activity, inducing expression of specific marker genes for both odontoblasts and osteoblasts while promoting hydroxyapatite production in both PPU7 and C2C12 cells. These responses were cell type specific. MDZ treatment alone could induce these changes in PPU7 cells, but C2C12 cell differentiation required BMP-2 addition.

Identifiants

DOI: 10.1016/j.job.2021.10.005 PMID: 34718143
pubmed: 34718143
pii: S1349-0079(21)00141-9
doi: 10.1016/j.job.2021.10.005
pii:
doi:

Substances chimiques

Bone Morphogenetic Proteins 0
Hydroxyapatites 0
Midazolam R60L0SM5BC

Types de publication

Journal Article Research Support, Non-U.S. Gov't Review

Langues

eng

Sous-ensembles de citation

IM

Pagination

37-42

Informations de copyright

Copyright © 2021 Japanese Association for Oral Biology. Published by Elsevier B.V. All rights reserved.

Déclaration de conflit d'intérêts

Conflict of interest The authors declare no potential conflicts of interest with respect to the authorship and/or publication of this article.

Auteurs

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. Electronic address: yamakoshi-y@tsurumi-u.ac.jp.

Risako Chiba-Ohkuma (R)

Department of Biochemistry and Molecular Biology, School of Dental Medicine, Tsurumi University, 2-1-3 Tsurumi, Tsurumi-ku, Yokohama 230-8501, Japan. Electronic address: chiba-r@tsurumi-u.ac.jp.

Yukihiko Hidaka (Y)

Hidaka Dental Clinic, 201 Shintsukagoshi, Saiwai-ku, Kawasaki 212-0027, Japan. Electronic address: hidaka.y55@gmail.com.

Kazuo Onuma (K)

Department of Biochemistry and Molecular Biology, School of Dental Medicine, Tsurumi University, 2-1-3 Tsurumi, Tsurumi-ku, Yokohama 230-8501, Japan. Electronic address: espkaz009@gmail.com.

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. Electronic address: yamamoto-rj@tsurumi-u.ac.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. Electronic address: saito-mari@tsurumi-u.ac.jp.

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. Electronic address: karakida-t@tsurumi-u.ac.jp.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Repurposing MDZ as a tool for tissue...
questionsmedicales.fr › Facteurs biologiques › Protéines et peptides de signalisation intercellulaire › Protéines de la superfamille du TGF bêta › Protéines morphogénétiques osseuses › Repurposing MDZ as a tool for tissue...
questionsmedicales.fr › Cellules › Cellules cultivées › Lignée cellulaire › Repurposing MDZ as a tool for tissue...
questionsmedicales.fr › Techniques d'investigation › Développement de médicament › Repositionnement des médicaments › Repurposing MDZ as a tool for tissue...
questionsmedicales.fr › Produits chimiques inorganiques › Composés du phosphore › Acides du phosphore › Acides phosphoriques › Phosphates › Phosphates de calcium › Apatites › Hydroxyapatites › Repurposing MDZ as a tool for tissue...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Repurposing MDZ as a tool for tissue...
questionsmedicales.fr › Composés hétérocycliques › Composés hétérocycliques à cycles fusionnés › Composés hétérobicycliques › Benzazépines › Benzodiazépines › Midazolam › Repurposing MDZ as a tool for tissue...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Artiodactyla › Suidae › Repurposing MDZ as a tool for tissue...