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Transgenic expression of dentin phosphoprotein inhibits skeletal development

H. Zhang, P. Liu, S. Wang, C. Liu, P. Jani, Y. Lu, C. Qin
  • H. Zhang
    Texas A&M University, Baylor College of Dentistry, United States
  • P. Liu
    Harbin Medical University School of Stomatology, China
  • S. Wang
    Texas A&M University, Baylor College of Dentistry, United States
  • C. Liu
    Texas A&M University, Baylor College of Dentistry, United States
  • P. Jani
    Texas A&M University, Baylor College of Dentistry, United States
  • Y. Lu
    Texas A&M University, Baylor College of Dentistry, United States
  • C. Qin
    Texas A&M University, Baylor College of Dentistry, United States | cqin@bcd.tamhsc.edu

Abstract

Dentin sialophosphoprotein (DSPP) is proteolytically processed into an NH2-terminal fragment called dentin sialoprotein (DSP) and a COOH-terminal fragment known as dentin phosphoprotein (DPP). These two fragments are believed to perform distinct roles in formation of bone and dentin. To investigate the functions of DPP in skeletal development, we generated transgenic mice to overexpress hemagglutinin (HA)-tagged DPP under the control of a 3.6 kb type I collagen (Col1a1) promoter (designated as Col1a1-HA-DPP). The Col1a1-HA-DPP transgenic mice were significantly smaller by weight, had smaller skeletons and shorter long bones than their wild type littermates, as demonstrated by X-ray radiography. They displayed reduced trabecular bone formation and narrower zones of proliferative and hypertrophic chondrocytes in the growth plates of the long bones. Histological analyses showed that the transgenic mice had reduced cell proliferation in the proliferating zone, but lacked obvious defects in the chondrocyte differentiation. In addition, the transgenic mice with a high level of transgene expression developed spontaneous long bone fractures. In conclusion, overexpressing DPP inhibited skeletal development, suggesting that the balanced actions between the NH2- and COOH-terminal fragments of DSPP may be required for normal skeletal development.

Keywords

Dentin sialophosphoprotein; dentin phosphoprotein; development; bone; transgenic mice; growth plate.

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Submitted: 2015-11-11 22:03:31
Published: 2016-03-11 10:22:06
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Copyright (c) 2016 H. Zhang, P. Liu, S. Wang, C. Liu, P. Jani, Y. Lu, C. Qin

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