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EGCG ameliorates the hypoxia-induced apoptosis and osteogenic differentiation reduction of mesenchymal stem cells via upregulating miR-210

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Abstract

The healing process of fractured bone is affected by the multiple factors regulating the growth and differentiation of osteoblasts and bone mesenchymal stem cells (MSCs), however, such markers and molecular events need to be orchestrated in details. This study investigated the effect of polyphenol(-)-epigallocatechin-3-gallate (EGCG) on the hypoxia-induced apoptosis and osteogenic differentiation of human bone marrow-derived MSCs, examined the miR-210 induction by EGCG, explored the target inhibition of the expression of receptor tyrosine kinase ligand ephrin-A3 (EFNA3) by miR-210, and then determined the association of the miR-210 promotion with the hypoxia-induced apoptosis and osteogenic differentiation. Results demonstrated that EGCG treatment significantly inhibited the hypoxia-induced apoptosis in MSCs and promoted the level of alkaline phosphatase (ALP), bone morphogenetic protein 2 (BMP-2), propeptide of type I procollagen I (PINP) and runt-related transcription factor 2 (RUNX2) in MSCs under either normoxia or hypoxia. Moreover, the EGCG treatment upregulated the miR-210 expression, in an association with EFNA3 downregulation; and the miR-210 upregulation significantly downregulated the expression of EFNA3 via the specific binding to the 3′ UTR of EFNA3. In addition, the manipulated miR-210 upregulation exerted amelioration on the hypoxia-induced apoptosis and on the hypoxia-reduced expression of ALP, BMP-2, PINP and RUNX2 in MSCs. In summary, our study indicated the protective role of EGCG in response to hypoxia and promontory role to osteogenic differentiation in MSCs via upregulating miR-210 and downregulating the expression of miR-210-targeted EFNA3. Our study implies the protective role of EGCG in the hypoxia-induced impairment in MSCs.

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Abbreviations

EGCG:

Polyphenol(-)-epigallocatechin-3-gallate

EFNA3:

Receptor tyrosine kinase ligand ephrin-A3

MSCs:

Mesenchymal stem cells

ALP:

Alkaline phosphatase

BMP-2:

Bone morphogenetic protein 2

PINP:

Propeptide of type I procollagen I

RUNX2:

Runt-related transcription factor 2

HIFs:

Hypoxia-inducible factors

VEGF:

Vascular endothelial growth factor

OPN:

Osteopontin

OCN:

Osteocalcin

PTP-1B:

Protein tyrosine phosphatase-1B

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Acknowledgments

Present study was supported by the Post-doctor Grant from the 2nd Shenzhen People’s Hospital (SZH2013006).

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Authors and Affiliations

  1. Department of Spine Surgery, The 2nd Shenzhen People’s Hospital, No. 3002, Sungang Road, Futian District, Shenzhen, 510000, China

    Yiyan Qiu, Yang Chen, Tenghui Zeng, Weizhuang Guo, Wenyu Zhou & Xinjian Yang

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  1. Yiyan Qiu
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  2. Yang Chen
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Correspondence to Xinjian Yang.

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Qiu, Y., Chen, Y., Zeng, T. et al. EGCG ameliorates the hypoxia-induced apoptosis and osteogenic differentiation reduction of mesenchymal stem cells via upregulating miR-210. Mol Biol Rep 43, 183–193 (2016). https://doi.org/10.1007/s11033-015-3936-0

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  • DOI: https://doi.org/10.1007/s11033-015-3936-0

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