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Int. J. Mol. Sci. 2018, 19(3), 734; https://doi.org/10.3390/ijms19030734

The Multiplicity of Infection-Dependent Effects of Recombinant Adenovirus Carrying HGF Gene on the Proliferation and Osteogenic Differentiation of Human Bone Marrow Mesenchymal Stem Cells

Institute of Molecular Immunology, School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou 510515, China
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Received: 22 December 2017 / Revised: 19 January 2018 / Accepted: 1 March 2018 / Published: 5 March 2018
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
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Abstract

Absence of effective therapeutic methods for avascular necrosis of femoral head (ANFH) is still perplexing the world’s medical community. Bone marrow mesenchymal stem cells (BMSCs) adoptive cell therapy combined with core decompression is a promising modality, which is highly dependent on the cellular activities of BMSCs. Hepatocyte growth factor (HGF) is a survival factor for BMSCs, yet the underlying mechanism is not fully elucidated. In this study, the effects of multiplicity of infections (MOIs) of recombinant adenovirus carrying HGF gene (rAd-HGF) on human BMSC proliferation and osteogenic differentiation were systemically examined. Infection of rAd-HGF produced secretory HGF and promoted hBMSC proliferation in a MOI-dependent manner, while the osteogenesis was also strengthened as indicated by enhanced calcium nodule formation with the strongest effects achieved at MOI = 250. Blocking the activities of c-MET or its downstream signaling pathways, WNT, ERK1/2, and PI3K/AKT led to differential consequents. Specifically, blockage of the WNT pathway significantly promoted osteogenic differentiation, which also showed additive effects when combined application with rAd-HGF. Our data demonstrated the pro-osteogenic effects of optimized MOIs of rAd-HGF, while inhibition of WNT pathway or activation of PI3K/AKT pathway may act as candidate adjuvant modalities for promoting osteogenic differentiation in rAd-HGF-modified hBMSC treatment on ANFH. View Full-Text
Keywords: avascular necrosis of femoral head; human bone marrow mesenchymal stem cell; hepatocyte growth factor; adenovirus; signaling pathway; proliferation; osteogenesis avascular necrosis of femoral head; human bone marrow mesenchymal stem cell; hepatocyte growth factor; adenovirus; signaling pathway; proliferation; osteogenesis
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Wen, Q.; Zhang, S.; Du, X.; Wang, R.; Li, Y.; Liu, H.; Hu, S.; Zhou, C.; Zhou, X.; Ma, L. The Multiplicity of Infection-Dependent Effects of Recombinant Adenovirus Carrying HGF Gene on the Proliferation and Osteogenic Differentiation of Human Bone Marrow Mesenchymal Stem Cells. Int. J. Mol. Sci. 2018, 19, 734.

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