title: Genipin, a cross-linking agent, promotes odontogenic differentiation of human dental pulp cells.
abstract: BACKGROUND
  The aim of this study was to investigate the effects of genipin, a natural collagen cross-linking agent, on odontogenic differentiation of human dental pulp cells (hDPCs) because the mechanical properties of collagen allow it to serve as a scaffold for engineering of pulp-dentin complex. Furthermore, the role of extracellular signal-regulated kinase (ERK) was investigated as a mediator of the differentiation.
  
  
  METHODS
  The odontogenic differentiation was analyzed by alkaline phosphatase activity, real time-polymerase chain reaction, Western blotting, and alizarin red S staining. The morphologic features of hDPCs cultured in genipin-treated collagen were evaluated by scanning electron microscopy. For the assessment of mechanical properties of collagen treated with genipin, the surface roughness and compressive strength were measured.
  
  
  RESULTS
  Alkaline phosphatase activity, the expression of odontogenic markers, and mineralized nodule formation increased in the genipin-treated group. Genipin also activated ERK, and treatment with ERK inhibitor blocked the expression of the markers. The cells cultured in genipin-treated collagen spread across the substrate and attached in close proximity to one another. The proliferation and differentiation of hDPCs cultured in genipin-treated collagen were facilitated. The mechanical properties of collagen, such as surface roughness and compressive strength, were increased by treatment with genipin.
  
  
  CONCLUSIONS
  Our results show that genipin promotes odontogenic differentiation of hDPCs via the ERK signaling pathway. Furthermore, the enhanced mechanical properties of the collagen scaffold induced by genipin may play important roles in cell fate. Consequently, the application of genipin might be a new strategy for dentin-pulp complex regeneration.
authors: Department of Conservative Dentistry, School of Dentistry and Institute of Oral Bioscience, Chonbuk National University, Jeonju, Korea.
authors: Young-Sun
authors: YS
authors: Kwon
authors: Department of Conservative Dentistry, School of Dentistry and Institute of Oral Bioscience, Chonbuk National University, Jeonju, Korea; Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute of Chonbuk National University Hospital, Jeonju, Korea.
authors: Eun-Su
authors: ES
authors: Lim
authors: Jeonbuk Institute for Bioindustry, Jeonju, Korea.
authors: Hye-Min
authors: HM
authors: Kim
authors: Department of Conservative Dentistry, School of Dentistry, Chonnam National University, Gwangju, Korea.
authors: Yun-Chan
authors: YC
authors: Hwang
authors: Department of Conservative Dentistry, School of Dentistry and Institute of Oral Bioscience, Chonbuk National University, Jeonju, Korea; Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute of Chonbuk National University Hospital, Jeonju, Korea.
authors: Kwang-Won
authors: KW
authors: Lee
authors: Department of Conservative Dentistry, School of Dentistry and Institute of Oral Bioscience, Chonbuk National University, Jeonju, Korea; Research Institute of Clinical Medicine of Chonbuk National University-Biomedical Research Institute of Chonbuk National University Hospital, Jeonju, Korea. Electronic address: endomin@gmail.com.
authors: Kyung-San
authors: KS
authors: Min
mesh_terms: D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003094:Collagen; D003432:Cross-Linking Reagents / Q000494:pharmacology*; D003782:Dental Pulp / Q000166:cytology / Q000187:drug effects*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D006801:Humans; D039823:Iridoids / Q000494:pharmacology*; D009805:Odontogenesis / Q000187:drug effects*; D010936:Plant Extracts / Q000494:pharmacology*; D019666:Rubiaceae / Q000737:chemistry
chemical_list: D003432:Cross-Linking Reagents; D039823:Iridoids; D010936:Plant Extracts; D003094:Collagen; C007834:genipin; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: Collagen; crosslinking; dental pulp cell; extracellular signal-regulated kinase; genipin; odontogenic differentiation