An Osteopontin-Integrin Interaction Plays a Critical Role in Directing Adipogenesis and Osteogenesis by Mesenchymal Stem Cells
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- Qing Chen
- Key Laboratory of Stem Cell Biology, Institute of Health Sciences Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences/Shanghai Jiao Tong University School of Medicine, Shanghai, China
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- Peishun Shou
- Key Laboratory of Stem Cell Biology, Institute of Health Sciences Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences/Shanghai Jiao Tong University School of Medicine, Shanghai, China
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- Liying Zhang
- Child Health Institute of New Jersey Robert Wood Johnson Medical School, New Brunswick, New Jersey, USA
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- Chunliang Xu
- Key Laboratory of Stem Cell Biology, Institute of Health Sciences Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences/Shanghai Jiao Tong University School of Medicine, Shanghai, China
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- Chunxing Zheng
- Key Laboratory of Stem Cell Biology, Institute of Health Sciences Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences/Shanghai Jiao Tong University School of Medicine, Shanghai, China
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- Yanyan Han
- Key Laboratory of Stem Cell Biology, Institute of Health Sciences Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences/Shanghai Jiao Tong University School of Medicine, Shanghai, China
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- Wenzhao Li
- Key Laboratory of Stem Cell Biology, Institute of Health Sciences Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences/Shanghai Jiao Tong University School of Medicine, Shanghai, China
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- Yin Huang
- Key Laboratory of Stem Cell Biology, Institute of Health Sciences Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences/Shanghai Jiao Tong University School of Medicine, Shanghai, China
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- Xiaoren Zhang
- Key Laboratory of Stem Cell Biology, Institute of Health Sciences Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences/Shanghai Jiao Tong University School of Medicine, Shanghai, China
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- Changshun Shao
- Department of Genetics The State University of New Jersey, Piscataway, New Jersey, USA
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- Arthur I. Roberts
- Child Health Institute of New Jersey Robert Wood Johnson Medical School, New Brunswick, New Jersey, USA
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- Arnold B. Rabson
- Child Health Institute of New Jersey Robert Wood Johnson Medical School, New Brunswick, New Jersey, USA
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- Guangwen Ren
- Child Health Institute of New Jersey Robert Wood Johnson Medical School, New Brunswick, New Jersey, USA
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- Yanyun Zhang
- Key Laboratory of Stem Cell Biology, Institute of Health Sciences Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences/Shanghai Jiao Tong University School of Medicine, Shanghai, China
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- Ying Wang
- Key Laboratory of Stem Cell Biology, Institute of Health Sciences Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences/Shanghai Jiao Tong University School of Medicine, Shanghai, China
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- David T. Denhardt
- Department of Cell Biology and Neuroscience, Rutgers The State University of New Jersey, Piscataway, New Jersey, USA
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- Yufang Shi
- Key Laboratory of Stem Cell Biology, Institute of Health Sciences Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences/Shanghai Jiao Tong University School of Medicine, Shanghai, China
書誌事項
- 公開日
- 2014-01-13
- 権利情報
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- https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model
- DOI
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- 10.1002/stem.1567
- 公開者
- Oxford University Press (OUP)
この論文をさがす
説明
<jats:title>Abstract</jats:title> <jats:p>An imbalance between normal adipogenesis and osteogenesis by mesenchymal stem cells (MSCs) has been shown to be related to various human metabolic diseases, such as obesity and osteoporosis; however, the underlying mechanisms remain elusive. We found that the interaction between osteopontin (OPN), an arginine-glycine-aspartate-containing glycoprotein, and integrin αv/β1 plays a critical role in the lineage determination of MSCs. Although OPN is a well-established marker during osteogenesis, its role in MSC differentiation is still unknown. Our study reveals that blockade of OPN function promoted robust adipogenic differentiation, while inhibiting osteogenic differentiation. Re-expression of OPN restored a normal balance between adipogenesis and osteogenesis in OPN−/− MSCs. Retarded bone formation by OPN−/− MSCs was also verified by in vivo implantation with hydroxyapatite-tricalcium phosphate, a bone-forming matrix. The role of extracellular OPN in MSC differentiation was further demonstrated by supplementation and neutralization of OPN. Blocking well-known OPN receptors integrin αv/β1 but not CD44 also affected MSC differentiation. Further studies revealed that OPN inhibits the C/EBPs signaling pathway through integrin αv/β1. Consistent with these in vitro results, OPN−/− mice had a higher fat to total body weight ratio than did wild-type mice. Therefore, our study demonstrates a novel role for OPN-integrin αv/β1 in regulating MSC differentiation. Stem Cells 2014;32:327–337</jats:p>
収録刊行物
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- Stem Cells
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Stem Cells 32 (2), 327-337, 2014-01-13
Oxford University Press (OUP)