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The Effect of Co-treating Human Mesenchymal Stem Cells with Epigallocatechin Gallate and Hypoxia-Inducible Factor-1 on the Expression of RANKL/RANK/OPG Signaling Pathway, Osteogenesis, and Angiogenesis Genes

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Abstract

Mesenchymal stem cells (MSCs) were considered the promising source in the regeneration of bone tissue. These cells have been known to have the ability to differentiate into the osteogenic lineage. The identification of the new approaches improved the efficiency of these cells in bone tissue engineering. In the present study, we investigated the combinational effect of epigallocatechin gallate (EGCG) and hypoxia-inducible factor-1 (HIF-1) on the osteogenic differentiation ability of human bone marrow-mesenchymal stem cells (BM-MSCs). Ten differently treated groups of BM-MSCs were evaluated by expression analysis of osteogenic and angiogenic markers including Runx2, COL1A1, SPARC, VEGF, and ALP as well as RANKL/RANK/OPG pathway genes. They included the experimental (cells treated with the culture medium containing 5, 10, and 20 μM EGCG with 15, 30, and 45 ng/ml HIF-1 or without HIF-1) and the control groups (untreated cells). The obtained results indicated that the co-treating with 5 μM EGCG+ 30 ng/ml HIF-1 increased the osteogenic ability of BM-MSCs as compared with the other experimental groups and the control cells. Furthermore, treatment with EGCG and HIF-1 showed to be associated with the RANKL upregulation as well as OPG downregulation. These observations suggested that HIF-1 improved the EGCG efficiency in the MSC differentiation into the osteogenic lineage.

Lay Summary

The administration of mesenchymal stem cells (MSCs) has been suggested to be a potential therapy tool in the repair of bone tissue. The identification of novel approaches could play an important role in the improvement of bone tissue engineering. In the present study, we investigated the effect of co-treating the human MSCs with epigallocatechin gallate (EGCG) and hypoxia-inducible factor-1 (HIF-1). The obtained results provided the better understanding about the effect of EGCG and HIF-1 on expression level of Runx2, COL1A1, SPARC, VEGF, ALP, OPG, and RANKL genes in the treated cells.

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Funding

The present study was financially supported by “Research Department of the School of Medicine Shahid Beheshti University of Medical Sciences” (Grant No 10489).

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Author notes

  1. Bahar Mohammadi and Zahra Esmaeilizade contributed equally to this work.

Authors and Affiliations

  1. Department of Medical Genetics, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Bahar Mohammadi, Zahra Esmaeilizade, Mir Davood Omrani, Sayyed Mohammad Hossein Ghaderian & Zahra Fazeli

  2. Department of Clinical Biochemistry, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Masoumeh Rajabibazl

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  1. Bahar Mohammadi
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Correspondence to Zahra Fazeli.

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The present study was approved by the Ethics Committee of the School of Medicine Shahid Beheshti University of Medical Sciences (Tehran, Iran; Ethical code: IR.SBMU.MSP.REC.1396.609).

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Mohammadi, B., Esmaeilizade, Z., Omrani, M.D. et al. The Effect of Co-treating Human Mesenchymal Stem Cells with Epigallocatechin Gallate and Hypoxia-Inducible Factor-1 on the Expression of RANKL/RANK/OPG Signaling Pathway, Osteogenesis, and Angiogenesis Genes. Regen. Eng. Transl. Med. 8, 117–124 (2022). https://doi.org/10.1007/s40883-021-00197-z

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