title: Eluted zinc ions stimulate osteoblast differentiation and mineralization in human dental pulp stem cells for bone tissue engineering.
abstract: OBJECTIVE
  Zinc is an essential element for proliferation, differentiation and survival in various cell types. In a previous study, we found that zinc ions released from zinc-modified titanium surfaces (eluted zinc ions; EZ) stimulate cell viability, osteoblast marker gene expression and calcium deposition in human bone marrow-derived mesenchymal cells (hBMCs). The aim of the present study was to investigate the effects of EZ on osteoblast differentiation among dental pulp stem cells (DPSCs) in vitro.
  
  
  METHODS
  In this study, we evaluated the effects of EZ on osteogenesis in DPSCs. Osteoblast and osteoclast marker gene expression was evaluated by real-time PCR. We also evaluated alkaline phosphatase (ALP) staining and calcium deposition.
  
  
  RESULTS
  We found that EZ stimulated osteoblast marker gene (type I collagen, alkaline phosphatase (ALP), osteocalcin (OCN) and Runx2) expression, vascular endothelial growth factor A (VEGF-A), and TGF-beta signaling pathway-related gene expression after 7days of incubation. Osteoclastogenesis occurs in a receptor for activated nuclear-factor kappa B ligand (RANKL)/osteoprotegerin (OPG)-independent manner. Real-time PCR analysis revealed that EZ did not affect RANKL or OPG mRNA expression. It was also revealed that EZ induced alkaline phosphatase (ALP) staining and calcium deposition in DPSCs. Collectively, these results demonstrate the potential for clinical application to prospective treatment of bone diseases.
authors: Department of Biochemistry, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita, Akita, 010-8543, Japan; Department of Dentistry, Oral and Maxillofacial-Plastic and Reconstructive Surgery, School of Medicine, Yamagata University, 2-2-2 Iida-Nishi, Yamagata, Yamagata, 990-9585, Japan. Electronic address: k-yusa@med.id.yamagata-u.ac.jp.
authors: Kazuyuki
authors: K
authors: Yusa
authors: Department of Bio-System Engineering, Graduate School of Science and Engineering, Yamagata University, 4-3-16 Johnan, Yonezawa, Yamagata, 992-8510, Japan.
authors: Osamu
authors: O
authors: Yamamoto
authors: Department of Dentistry, Oral and Maxillofacial-Plastic and Reconstructive Surgery, School of Medicine, Yamagata University, 2-2-2 Iida-Nishi, Yamagata, Yamagata, 990-9585, Japan.
authors: Mitsuyoshi
authors: M
authors: Iino
authors: Division of Dentistry and Oral Surgery, Akita University School of Medicine, 1-1-1 Hondo, Akita, Akita, 010-8543, Japan.
authors: Hiroshi
authors: H
authors: Takano
authors: Division of Dentistry and Oral Surgery, Akita University School of Medicine, 1-1-1 Hondo, Akita, Akita, 010-8543, Japan.
authors: Masayuki
authors: M
authors: Fukuda
authors: Department of Biochemistry, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita, Akita, 010-8543, Japan.
authors: Zhiwei
authors: Z
authors: Qiao
authors: Department of Biochemistry, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita, Akita, 010-8543, Japan.
authors: Toshihiro
authors: T
authors: Sugiyama
mesh_terms: D000469:Alkaline Phosphatase / Q000096:biosynthesis; D001861:Bone Regeneration / Q000187:drug effects*; D002454:Cell Differentiation / Q000187:drug effects*; D024042:Collagen Type I / Q000096:biosynthesis; D050659:Core Binding Factor Alpha 1 Subunit / Q000096:biosynthesis; D003782:Dental Pulp / Q000166:cytology*; D015870:Gene Expression; D006801:Humans; D066298:In Vitro Techniques; D007477:Ions / Q000494:pharmacology; D059630:Mesenchymal Stem Cells / Q000187:drug effects*; D010006:Osteoblasts / Q000187:drug effects*; D015675:Osteocalcin / Q000096:biosynthesis; D010012:Osteogenesis / Q000187:drug effects*; D060888:Real-Time Polymerase Chain Reaction; D023822:Tissue Engineering / Q000379:methods*; D014025:Titanium / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000096:biosynthesis; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis; D015032:Zinc / Q000494:pharmacology*
chemical_list: D024042:Collagen Type I; D050659:Core Binding Factor Alpha 1 Subunit; D007477:Ions; D016212:Transforming Growth Factor beta; D042461:Vascular Endothelial Growth Factor A; D015675:Osteocalcin; D014025:Titanium; D000469:Alkaline Phosphatase; D015032:Zinc
keywords: Bone tissue engineering; Dental pulp stem cells; Osteoblast differentiation; Zinc ion; Zinc-modified titanium