Experimental and Molecular Medicine

Korean Society for Biochemistry and Molecular Biongy (생화학분자생물학회)
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Elevated extracellular calcium ions promote proliferation and migration of mesenchymal stem cells via increasing osteopontin expression

  • Lee, Mi Nam (Research Center for Biomineralization Disorders, School of Dentistry, Chonnam National University) ;
  • Hwang, Hee-Su (Research Center for Biomineralization Disorders, School of Dentistry, Chonnam National University) ;
  • Oh, Sin-Hye (Research Center for Biomineralization Disorders, School of Dentistry, Chonnam National University) ;
  • Roshanzadeh, Amir (School of Biological Sciences and Biotechnology, Chonnam National University) ;
  • Kim, Jung-Woo (Research Center for Biomineralization Disorders, School of Dentistry, Chonnam National University) ;
  • Song, Ju Han (Research Center for Biomineralization Disorders, School of Dentistry, Chonnam National University) ;
  • Kim, Eung-Sam (Department of Biological Sciences, Chonnam National University) ;
  • Koh, Jeong-Tae (Research Center for Biomineralization Disorders, School of Dentistry, Chonnam National University)
  • Received : 2018.02.21
  • Accepted : 2018.07.12
  • Published : 2018.11.30
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Abstract

Supplementation of mesenchymal stem cells (MSCs) at sites of bone resorption is required for bone homeostasis because of the non-proliferation and short lifespan properties of the osteoblasts. Calcium ions ($Ca^{2+}$) are released from the bone surfaces during osteoclast-mediated bone resorption. However, how elevated extracellular $Ca^{2+}$ concentrations would alter MSCs behavior in the proximal sites of bone resorption is largely unknown. In this study, we investigated the effect of extracellular $Ca^{2+}$ on MSCs phenotype depending on $Ca^{2+}$ concentrations. We found that the elevated extracellular $Ca^{2+}$ promoted cell proliferation and matrix mineralization of MSCs. In addition, MSCs induced the expression and secretion of osteopontin (OPN), which enhanced MSCs migration under the elevated extracellular $Ca^{2+}$ conditions. We developed in vitro osteoclast-mediated bone resorption conditions using mouse calvaria bone slices and demonstrated $Ca^{2+}$ is released from bone resorption surfaces. We also showed that the MSCs phenotype, including cell proliferation and migration, changed when the cells were treated with a bone resorption-conditioned medium. These findings suggest that the dynamic changes in $Ca^{2+}$ concentrations in the microenvironments of bone remodeling surfaces modulate MSCs phenotype and thereby contribute to bone regeneration.

Keywords

Acknowledgement

Supported by : National Research Foundation of Korea (NRF)

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