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.
Highlights
Zirconium (Zr) is one of the more common trace elements present in the environment [1]
We further demonstrated that Baghdadite scaffolds can modulate the crosstalk between adipose stem cells (ASCs) and primary human osteoblasts (HOBs) to promote osteogenic gene expression in both ASCs and HOBs in an indirect co-culture system [8]
HOBs at Passage 3 were treated with ZrO(NO3)2 or ZrCl4 solutions at the final concentrations in the medium of 5, 50 and 500 μM and incubated for 1, 3 and 7 days, while the complete medium or NaNO3 solution at 50 μM in medium was used as an untreated control and a control for the nitrate content of ZrO(NO3)2
Summary
Zirconium (Zr) is one of the more common trace elements present in the environment [1]. It is a metallic element with a valency of 4 that is normally present in human bone and tissues at a trace level in the range 2–20 mg/kg body weight with an estimated average daily intake in humans of 3.5 mg [1]. Toxicity of Zr has been assessed as low to moderate in animals [1]. Predominantly as the stable and biologically inert zirconium oxide (ZrO2) and metal alloys, have been widely used in dental applications and as coatings for PLOS ONE | DOI:10.1371/journal.pone.0113426. Predominantly as the stable and biologically inert zirconium oxide (ZrO2) and metal alloys, have been widely used in dental applications and as coatings for PLOS ONE | DOI:10.1371/journal.pone.0113426 January 20, 2015
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