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Effects of Zinc Transporter on Differentiation of Bone Marrow Mesenchymal Stem Cells to Osteoblasts

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Abstract

The differentiation of bone marrow mesenchymal stem cells (MSCs) into osteoblasts is a crucial step during bone formation. However, the exact mechanisms regulating the early stages of osteogenic differentiation remain unknown. In the present study, we found that ZnT7, a member of the zinc transporter family SLC30A(ZnTs), was downregulated during dexamethasone-induced differentiation of rat MSCs into osteoblasts. Dexamethasone treatment resulted in significantly lower levels of ZnT7 compared with cocultured cells without dexamethasone. Differentiation was evaluated by measuring alkaline phosphatase (ALP) activity and staining for ALP, von Kossa, collagen type I, and osteocalcin. Overexpression of ZnT7 decreased the expression of the osteoblast alkaline phosphatase, type I collagen, as well as calcium deposition in mesenchymal cells. In contrast, knockdown of ZnT7 using siRNA promoted gene expression associated with osteoblast differentiation and matrix mineralization in vitro. Moreover, according to the ZnT7 inhibition or activation experiments, Wnt and ERK signaling pathways were found to be important signal transduction pathways in mediating the osteogenic effect of MSCs, and this effect is intensified by a decrease in the level of ZnT7 induced by dexamethasone. These findings suggest that ZnT7 is involved in the switch from the undifferentiated state of MSC to an osteogenic program, and marking the expression level of ZnT7 may be useful in the detection of early osteogenic differentiation.

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Abbreviations

MSCs:

Mesenchymal stem cells

ZnT:

Zinc transporter

D-MEM:

D-minimal essential medium

FITC:

Fluorescein isothiocyanate

PBS:

Phosphate-buffered saline

TBS:

Tris-buffered saline

PI:

Propidium iodide

MAPK:

Mitogen-activated protein kinase

ERK:

Extracellular signal-regulated kinase

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Authors and Affiliations

  1. The First Affiliated Hospital of Harbin Medical University, 23 You Zheng Street, Harbin, 150001, China

    Yang Liu, Feng Yan, Wei-Liang Yang, Xiao-Feng Lu & Wen-Bo Wang

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  1. Yang Liu
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  2. Feng Yan
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  3. Wei-Liang Yang
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  4. Xiao-Feng Lu
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Correspondence to Wen-Bo Wang.

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Liu, Y., Yan, F., Yang, WL. et al. Effects of Zinc Transporter on Differentiation of Bone Marrow Mesenchymal Stem Cells to Osteoblasts. Biol Trace Elem Res 154, 234–243 (2013). https://doi.org/10.1007/s12011-013-9683-y

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  • DOI: https://doi.org/10.1007/s12011-013-9683-y

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