title: Zirconium ions up-regulate the BMP/SMAD signaling pathway and promote the proliferation and differentiation of human osteoblasts.
abstract: Zirconium (Zr) is an element commonly used in dental and orthopedic implants either as zirconia (ZrO2) or in metal alloys. It can also be incorporated into calcium silicate-based ceramics. However, the effects of in vitro culture of human osteoblasts (HOBs) with soluble ionic forms of Zr have not been determined. In this study, primary culture of human osteoblasts was conducted in the presence of medium containing either ZrCl4 or Zirconium (IV) oxynitrate (ZrO(NO3)2) at concentrations of 0, 5, 50 and 500 µM, and osteoblast proliferation, differentiation and calcium deposition were assessed. Incubation of human osteoblast cultures with Zr ions increased the proliferation of human osteoblasts and also gene expression of genetic markers of osteoblast differentiation. In 21 and 28 day cultures, Zr ions at concentrations of 50 and 500 µM increased the deposition of calcium phosphate. In addition, the gene expression of BMP2 and BMP receptors was increased in response to culture with Zr ions and this was associated with increased phosphorylation of SMAD1/5. Moreover, Noggin suppressed osteogenic gene expression in HOBs co-treated with Zr ions. In conclusion, Zr ions appear able to induce both the proliferation and the differentiation of primary human osteoblasts. This is associated with up-regulation of BMP2 expression and activation of BMP signaling suggesting this action is, at least in part, mediated by BMP signaling.
authors.affiliation: Biomaterials and Tissue Engineering Research Unit, School of AMME, The University of Sydney, Sydney, New South Wales 2006, Australia.
authors.forename: Yongjuan
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Biomaterials and Tissue Engineering Research Unit, School of AMME, The University of Sydney, Sydney, New South Wales 2006, Australia.
authors.forename: Seyed-Iman
authors.initials: SI
authors.lastname: Roohani-Esfahani
authors.affiliation: Biomaterials and Tissue Engineering Research Unit, School of AMME, The University of Sydney, Sydney, New South Wales 2006, Australia.
authors.forename: ZuFu
authors.initials: Z
authors.lastname: Lu
authors.affiliation: Biomaterials and Tissue Engineering Research Unit, School of AMME, The University of Sydney, Sydney, New South Wales 2006, Australia.
authors.forename: Hala
authors.initials: H
authors.lastname: Zreiqat
authors.affiliation: Biomaterials and Tissue Engineering Research Unit, School of AMME, The University of Sydney, Sydney, New South Wales 2006, Australia.
authors.forename: Colin R
authors.initials: CR
authors.lastname: Dunstan
mesh_terms: D055396:Bone Morphogenetic Protein 2 / Q000235:genetics; D052004:Bone Morphogenetic Protein Receptors / Q000235:genetics; D019485:Bone Morphogenetic Proteins / Q000378:metabolism*; D002113:Calcification, Physiologic / Q000187:drug effects; D002352:Carrier Proteins / Q000378:metabolism; D002454:Cell Differentiation; D049109:Cell Proliferation / Q000187:drug effects; D002712:Chlorides / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D005819:Genetic Markers; D006801:Humans; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D010012:Osteogenesis / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects*; D051785:Smad Proteins / Q000378:metabolism*; D015040:Zirconium / Q000494:pharmacology*; D000099176:Noggin Protein
chemical_list: D055396:Bone Morphogenetic Protein 2; D052004:Bone Morphogenetic Protein Receptors; D019485:Bone Morphogenetic Proteins; D002352:Carrier Proteins; D002712:Chlorides; D005819:Genetic Markers; D051785:Smad Proteins; D015040:Zirconium; D000099176:Noggin Protein; C429984:zirconium chloride