Human Amnion-Derived Mesenchymal Stem Cells Promote Osteogenic Differentiation in Human Bone Marrow Mesenchymal Stem Cells by Influencing the ERK1/2 Signaling Pathway.

Yuli Wang,Yi Liang,Ning Chen,Fei Jiang,Ming Shen

doi:10.1155/2016/4851081

Abstract

Human amnion-derived mesenchymal stem cells (HAMSCs) are considered to be an important resource in the field of tissue engineering because of their anti-inflammatory properties and fewer ethical issues associated with their use compared with other sources of stem cells. HAMSCs can be obtained from human amniotic membranes, a readily available and abundant tissue. However, the potential of HAMSCs as seed cells for treating bone deficiency is unknown. In this study, HAMSCs were used to promote proliferation and osteoblastic differentiation in human bone marrow mesenchymal stem cells (HBMSCs) in a Transwell coculture system. Proliferation levels were investigated by flow cytometry and immunofluorescence staining of 5-ethynyl-2′-deoxyuridine (EdU). Osteoblastic differentiation and mineralization were evaluated in chromogenic alkaline phosphatase (ALP) activity substrate assays, Alizarin red S staining, and RT-PCR analysis of early HBMSCs osteogenic marker expression. We demonstrated that HAMSCs stimulated increased alkaline phosphatase (ALP) activity, mRNA expression of osteogenic marker genes, and mineralized matrix deposition. Moreover, the effect of HAMSCs was significantly inhibited by U0126, a highly selective inhibitor of extracellular signaling-regulated kinase 1/2 (ERK1/2) signaling. We demonstrate that HAMSCs promote osteogenic differentiation in HBMSCs by influencing the ERK1/2 signaling pathway. These observations confirm the potential of HAMSCs as a seed cell for the treatment of bone deficiency.

Highlights

An emerging medical and socioeconomic problem among patients requiring dental implants is bone volume inadequacy, which increases the difficulty of restoring oral function
Recent studies showed that Human amnion-derived mesenchymal stem cells (HAMSCs) osteogenesis was much lower than other marrow mesenchymal stem cells’ [8], the acellular amniotic membrane matrix was capable of enhancing osteogenic differentiation in dental pulp stem cells (DPSCs) by activating extracellular signaling-regulated kinase 1/2 (ERK1/2) signaling [9], which led us to hypothesize that the function of HAMSCs in tissue-engineered bone is derived from its effect on other cells
We further investigated the role of the ERK1/2 signaling pathway in osteogenic differentiation in Human bone marrow mesenchymal stem cells (HBMSCs) cocultured with HAMSCs

Summary

Introduction

An emerging medical and socioeconomic problem among patients requiring dental implants is bone volume inadequacy, which increases the difficulty of restoring oral function. Human bone marrow mesenchymal stem cells (HBMSCs), osteoblasts (OB), and dental pulp stem cells (DPSCs) have been used as seed cells [1,2,3], but most have disadvantages, such as high immunogenicity and limited availability. Human amnion-derived mesenchymal stem cells (HAMSCs) are associated with low anti-inflammatory properties and fewer ethical issues than other sources of stem cells, providing considerable benefits as seed cells in bone tissue engineering [7]. Recent studies showed that HAMSC osteogenesis was much lower than other marrow mesenchymal stem cells’ [8], the acellular amniotic membrane matrix was capable of enhancing osteogenic differentiation in DPSCs by activating ERK1/2 signaling [9], which led us to hypothesize that the function of HAMSCs in tissue-engineered bone is derived from its effect on other cells.

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