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Esben Skipper Sørensen

Osteopontin mediates mineralization and not osteogenic cell development in vitro

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  • Erik Holm, Department of Biochemistry, Schulich School of Medicine & Dentistry, University of Western Ontario, London, Ontario, Canada, Canada
  • Jared S Gleberzon, Department of Biochemistry, Schulich School of Medicine & Dentistry, University of Western Ontario, London, Ontario, Canada, Canada
  • Yinyin Liao, Department of Biochemistry, Schulich School of Medicine & Dentistry, University of Western Ontario, London, Ontario, Canada, Canada
  • Esben Skipper Sørensen
  • Frank Beier, Department of Physiology and Pharmacology, Schulich School of Medicine & Dentistry, University of Western Ontario, London, Ontario, Canada, Canada
  • Graeme K Hunter, School of Dentistry, Schulich School of Medicine & Dentistry, University of Western Ontario, London, Ontario, Canada, Department of Biochemistry, Schulich School of Medicine & Dentistry, University of Western Ontario, London, Ontario, Canada, Canada
  • Graeme K Hunter, Department of Biochemistry, Schulich School of Medicine & Dentistry, University of Western Ontario, London, Ontario, Canada, School of Dentistry, Schulich School of Medicine & Dentistry, University of Western Ontario, London, Ontario, Canada, Canada

Biomineralization is a complex process in the development of mineralized tissues such as bone, and pathological calcifications such as atherosclerotic plaques, kidney stones, gout, and others. Osteopontin (OPN), an anionic phosphoprotein, is expressed in mineralizing tissues and has previously been demonstrated to be a potent inhibitor of hydroxyapatite formation. The OPN-deficient (Opn-/-) mouse displays a hypermineralized bone phenotype starting at 12 weeks post-natally. By isolating and culturing Opn-/- and wild-type (WT) osteoblasts, we sought to determine the role of OPN and two of its functional peptides in osteoblast development and mineralization. Opn-/- osteoblasts had significantly increased mineral deposition relative to their WT counterparts, with no physiologically relevant change in gene expression of osteogenic markers. Supplementation with bovine milk OPN (mOPN) led to a dramatic reduction in mineral deposition by the Opn-/- osteoblasts. Treatment with OPN peptides corresponding to phosphorylated OPN220-235 (P3) and non-phosphorylated OPN65-80 (OPAR) also rescued the hypermineralization phenotype of Opn-/- osteogenic cultures. Supplementation with mOPN or the OPN-derived peptides did not alter the expression of terminal osteogenic markers. These data suggest that OPN plays an important role in the regulation of biomineralization, but does not appear to affect osteoblast cell development in vitro.

Original languageEnglish
JournalBiochemical Journal
Volume464
Issue3
Pages (from-to)355-364
Number of pages10
ISSN0264-6021
DOIs
Publication statusPublished - Oct 2014

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