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https://hdl.handle.net/2440/66469
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Type: | Journal article |
Title: | Pharmacologic stem cell based intervention as a new approach to osteoporosis treatment in rodents |
Author: | Yamaza, T. Miura, I. Bi, Y. Liu, Y. Akiyama, K. Sonoyama, W. Patel, Y. Gutkind, S. Young, M. Gronthos, S. Le, A. Wang, C. Chen, W. Shi, S. |
Citation: | PLoS One, 2008; 3(7):1-9 |
Publisher: | Public Library of Science |
Issue Date: | 2008 |
ISSN: | 1932-6203 1932-6203 |
Editor: | Zwaka, T. |
Statement of Responsibility: | Takayoshi Yamaza, Yasuo Miura, Yanming Bi, Yongzhong Liu, Kentaro Akiyama, Wataru Sonoyama, Voymesh Patel, Silvio Gutkind, Marian Young, Stan Gronthos, Anh Le, Cun-Yu Wang, WanJun Chen and Songtao Shi |
Abstract: | Background: Osteoporosis is the most prevalent skeletal disorder, characterized by a low bone mineral density (BMD) and bone structural deterioration, leading to bone fragility fractures. Accelerated bone resorption by osteoclasts has been established as a principal mechanism in osteoporosis. However, recent experimental evidences suggest that inappropriate apoptosis of osteoblasts/osteocytes accounts for, at least in part, the imbalance in bone remodeling as occurs in osteoporosis. The aim of this study is to examine whether aspirin, which has been reported as an effective drug improving bone mineral density in human epidemiology studies, regulates the balance between bone resorption and bone formation at stem cell levels. Methods and Findings: We found that T cell-mediated bone marrow mesenchymal stem cell (BMMSC) impairment plays a crucial role in ovariectomized-induced osteoporosis. Ex vivo mechanistic studies revealed that T cell-mediated BMMSC impairment was mainly attributed to the apoptosis of BMMSCs via the Fas/Fas ligand pathway. To explore potential of using pharmacologic stem cell based intervention as an approach for osteoporosis treatment, we selected ovariectomy (OVX)- induced ostoeporosis mouse model to examine feasibility and mechanism of aspirin-mediated therapy for osteoporosis. We found that aspirin can inhibit T cell activation and Fas ligand induced BMMSC apoptosis in vitro. Further, we revealed that aspirin increases osteogenesis of BMMSCs by aiming at telomerase activity and inhibits osteoclast activity in OVX mice, leading to ameliorating bone density. Conclusion: Our findings have revealed a novel osteoporosis mechanism in which activated T cells induce BMMSC apoptosis via Fas/Fas ligand pathway and suggested that pharmacologic stem cell based intervention by aspirin may be a new alternative in osteoporosis treatment including activated osteoblasts and inhibited osteoclasts. |
Keywords: | T-Lymphocytes CD4-Positive T-Lymphocytes Bone Marrow Cells Osteoclasts Mesenchymal Stem Cells Animals Mice, Inbred C3H Mice, Transgenic Humans Mice Osteoporosis Bone Resorption Aspirin Mesenchymal Stem Cell Transplantation Apoptosis Interleukin-2 Receptor alpha Subunit |
Rights: | Copyright 2008 Yamaza 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. |
DOI: | 10.1371/journal.pone.0002615 |
Published version: | http://dx.doi.org/10.1371/journal.pone.0002615 |
Appears in Collections: | Aurora harvest Medicine publications |
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hdl_66469.pdf | Published version | 1.59 MB | Adobe PDF | View/Open |
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