Repurposing MDZ as a tool for tissue regeneration in dental cells |
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| Affiliation: | 1. Department of Biochemistry and Molecular Biology, School of Dental Medicine, Tsurumi University, 2-1-3 Tsurumi, Tsurumi-ku, Yokohama 230-8501, Japan;2. Hidaka Dental Clinic, 201 Shintsukagoshi, Saiwai-ku, Kawasaki 212-0027, Japan;1. Department of Oral Functional Anatomy, Hokkaido University Faculty of Dental Medicine, Kita 13, Nishi 7, Kita-ku, Sapporo 060-8586, Japan;2. Division of Pharmacology, Department of Oral Biology, School of Dentistry, Health Sciences University of Hokkaido, Ishikari-Tobetsu 061-0293, Japan;1. Monell Chemical Senses Center, 3500 Market Street, Philadelphia, PA 19104, USA;2. Department of Oral Physiology, Asahi University School of Dentistry, 1851-1 Hozumi, Mizuho, Gifu 501-0296, Japan;3. Obesity Institute, Geisinger Medical Center, 100 North Academy Ave, Danville, PA 17822, USA;4. Graduate School of Dental Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582 Japan;5. Oral Health Science Center, Tokyo Dental College, 2-9-18 Kandamisaki-cho, Chiyoda-ku, Tokyo 101-0061 Japan;6. Department of Oral Physiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 2-5-1, Shikata-cho, Kita-ku, Okayama, 700-8558 Japan;1. Division of Forensic Odontology, Department of Diagnostic ＆ Therapeutic Sciences, Meikai University School of Dentistry, Saitama, Japan;2. Division of Dental Radiology, Department of Diagnostic ＆ Therapeutic Sciences, Meikai University School of Dentistry, Saitama, Japan;3. Forensic Odontology Center, Meikai University School of Dentistry, Saitama, Japan;4. Department of Legal Medicine, Nihon University School of Dentistry, Tokyo, Japan;1. Department of Anatomy, Nihon University School of Dentistry at Matsudo, 2-870-1 Sakaecho Nishi, Matsudo City, Chiba 271-8587, Japan;2. Department of Precision Machinery Engineering, Nihon University College of Science and Technology, 7-24-1 Narashinodai, Funabashi City, Chiba 274-8501, Japan |
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| Abstract: | BackgroundSeveral 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.HighlightsWe 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.ConclusionMDZ 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. |
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| Keywords: | Drug repurposing Dental pulp Midazolam Osteoblast Hydroxyapatite |
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