RESEARCH ARTICLE
Effects of Iron Overload on the Bone Marrow Microenvironment in Mice Yuchen Zhang1☯, Wenjing Zhai2☯, Mingfeng Zhao1*, Deguan Li3, Xiao Chai1, Xiaoli Cao1¤, Juanxia Meng1, Jie Chen1, Xia Xiao1, Qing Li1, Juan Mu1, Jichun Shen4, Aimin Meng3 1 Department of Hematology, Tianjin First Central Hospital, Tianjin, China, 2 Department of Stem Cells Transplantation, Blood Disease Hospital of Chinese Academy of Medical Sciences, Tianjin, China, 3 Key Lab of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Academy of Medical Science and Peking Union Medical College, Tianjin, China, 4 Department of Hematology, Affiliated Hospital of Logistics University of People’s Armed Police Force, Tianjin, China ☯ These authors contributed equally to this work. ¤ Current Address: Department of Hematology, Tianjin First Central Hospital, No. 24 Fu Kang Road, Tianjin, China *
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Abstract OPEN ACCESS Citation: Zhang Y, Zhai W, Zhao M, Li D, Chai X, Cao X, et al. (2015) Effects of Iron Overload on the Bone Marrow Microenvironment in Mice. PLoS ONE 10(3): e0120219. doi:10.1371/journal.pone.0120219 Academic Editor: Eva Mezey, National Institutes of Health, UNITED STATES Received: November 10, 2014 Accepted: January 20, 2015 Published: March 16, 2015 Copyright: © 2015 Zhang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability Statement: All relevant data are within the paper and its Supporting Information files. Funding: This study was supported by the National Natural Science Foundation of China (81041043), the National Natural Science Foundation of Tianjin (13JCYBJC23400), and Science and Technique Foundation of Tianjin (13KG106,2013KR07). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist.
Objective Using a mouse model, Iron Overload (IO) induced bone marrow microenvironment injury was investigated, focusing on the involvement of reactive oxygen species (ROS).
Methods Mice were intraperitoneally injected with iron dextran (12.5, 25, or 50mg) every three days for two, four, and six week durations. Deferasirox(DFX)125mg/ml and N-acetyl-L-cysteine (NAC) 40mM were co-administered. Then, bone marrow derived mesenchymal stem cells (BM-MSCs) were isolated and assessed for proliferation and differentiation ability, as well as related gene changes. Immunohistochemical analysis assessed the expression of haematopoietic chemokines. Supporting functions of BM-MSCs were studied by coculture system.
Results In IO condition (25mg/ml for 4 weeks), BM-MSCs exhibited proliferation deficiencies and unbalanced osteogenic/adipogenic differentiation. The IO BM-MSCs showed a longer double time (2.07±0.14 days) than control (1.03±0.07 days) (P
