Distinct roles of bone morphogenetic proteins in osteogenic differentiation of mesenchymal stem cells

Authors

  • Hue H. Luu,

    1. Molecular Oncology Laboratory, Department of Surgery, 5841 South Maryland Avenue, MC 3079, Room J-611, The University of Chicago Medical Center, Chicago, Illinois 60637
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  • Wen-Xin Song,

    1. Molecular Oncology Laboratory, Department of Surgery, 5841 South Maryland Avenue, MC 3079, Room J-611, The University of Chicago Medical Center, Chicago, Illinois 60637
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  • Xiaoji Luo,

    1. Molecular Oncology Laboratory, Department of Surgery, 5841 South Maryland Avenue, MC 3079, Room J-611, The University of Chicago Medical Center, Chicago, Illinois 60637
    2. Key Laboratory of Diagnostic Medicine Designated by Ministry of Education and The Affiliated Hospitals, Chongqing University of Medical Sciences, Chongqing, China
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  • David Manning,

    1. Molecular Oncology Laboratory, Department of Surgery, 5841 South Maryland Avenue, MC 3079, Room J-611, The University of Chicago Medical Center, Chicago, Illinois 60637
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  • Jinyong Luo,

    1. Molecular Oncology Laboratory, Department of Surgery, 5841 South Maryland Avenue, MC 3079, Room J-611, The University of Chicago Medical Center, Chicago, Illinois 60637
    2. Key Laboratory of Diagnostic Medicine Designated by Ministry of Education and The Affiliated Hospitals, Chongqing University of Medical Sciences, Chongqing, China
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  • Zhong-Liang Deng,

    1. Molecular Oncology Laboratory, Department of Surgery, 5841 South Maryland Avenue, MC 3079, Room J-611, The University of Chicago Medical Center, Chicago, Illinois 60637
    2. Key Laboratory of Diagnostic Medicine Designated by Ministry of Education and The Affiliated Hospitals, Chongqing University of Medical Sciences, Chongqing, China
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  • Katie A. Sharff,

    1. Molecular Oncology Laboratory, Department of Surgery, 5841 South Maryland Avenue, MC 3079, Room J-611, The University of Chicago Medical Center, Chicago, Illinois 60637
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  • Anthony G. Montag,

    1. Molecular Oncology Laboratory, Department of Surgery, 5841 South Maryland Avenue, MC 3079, Room J-611, The University of Chicago Medical Center, Chicago, Illinois 60637
    2. Department of Pathology, The University of Chicago Medical Center, Chicago, Illinois 60637
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  • Rex C. Haydon,

    1. Molecular Oncology Laboratory, Department of Surgery, 5841 South Maryland Avenue, MC 3079, Room J-611, The University of Chicago Medical Center, Chicago, Illinois 60637
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  • Tong-Chuan He

    Corresponding author
    1. Molecular Oncology Laboratory, Department of Surgery, 5841 South Maryland Avenue, MC 3079, Room J-611, The University of Chicago Medical Center, Chicago, Illinois 60637
    2. Key Laboratory of Diagnostic Medicine Designated by Ministry of Education and The Affiliated Hospitals, Chongqing University of Medical Sciences, Chongqing, China
    • Molecular Oncology Laboratory, Department of Surgery, 5841 South Maryland Avenue, MC 3079, Room J-611, The University of Chicago Medical Center, Chicago, Illinois 60637. Telephone: 773-702-7169; Fax: 773-834-4598.
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  • Rex C. Haydon and Tong-Chuan He are recipients of the 2006 Kappa Delta's Ann Donor Vaughan Award.

Abstract

Efficacious bone regeneration could revolutionize the clinical management of many bone and musculoskeletal disorders. Bone morphogenetic proteins (BMPs) can regulate the differentiation of mesenchymal stem cells into cartilage, bone, tendon/ligament, and fat lineages. Early data documented the osteogenic potential of rhBMP2 and rhBMP7/OP-1. However, prior to this work that summarized several of our recent studies, no comprehensive analysis had been undertaken to characterize relative osteogenic activity of all BMPs. Using recombinant adenoviruses expressing 14 BMPs, we have demonstrated that, besides BMP2 and BMP7, BMP6 and BMP9 exhibit the highest osteogenic activity both in vitro and in vivo. We further demonstrated that several BMPs may exert synergistic effect on osteogenic differentiation, and that osteogenic BMPs produce a distinct set of molecular fingerprints during osteogenic differentiation. The reported work should expand our current understanding of BMP functions during osteogenic differentiation. It is conceivable that osteogenic BMPs (i.e., BMP2, 4, 6, 7, and 9) may be used to formulate synergistic pairs among themselves and/or with other less osteogenic BMPs for efficacious bone regeneration in clinical settings. © 2007 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 25:665–677, 2007

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