An Osteopontin-Integrin Interaction Plays a Critical Role in Directing Adipogenesis and Osteogenesis by Mesenchymal Stem Cells

  • 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
  • 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
  • Liying Zhang
    Child Health Institute of New Jersey Robert Wood Johnson Medical School, New Brunswick, New Jersey, USA
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • Changshun Shao
    Department of Genetics The State University of New Jersey, Piscataway, New Jersey, USA
  • Arthur I. Roberts
    Child Health Institute of New Jersey Robert Wood Johnson Medical School, New Brunswick, New Jersey, USA
  • Arnold B. Rabson
    Child Health Institute of New Jersey Robert Wood Johnson Medical School, New Brunswick, New Jersey, USA
  • Guangwen Ren
    Child Health Institute of New Jersey Robert Wood Johnson Medical School, New Brunswick, New Jersey, USA
  • 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
  • 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
  • David T. Denhardt
    Department of Cell Biology and Neuroscience, Rutgers The State University of New Jersey, Piscataway, New Jersey, USA
  • 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
  • https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model
DOI
  • 10.1002/stem.1567
公開者
Oxford University Press (OUP)

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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

  • Stem Cells

    Stem Cells 32 (2), 327-337, 2014-01-13

    Oxford University Press (OUP)

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