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Journal of Cellular Biochemistry

NELL-1 promotes cell adhesion and differentiation via integrinβ1

Authors

  • Jia Shen,

    1. Dental and Craniofacial Research Institute and Section of Orthodontics, School of Dentistry, University of California, Los Angeles, Los Angeles, California 90095
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  • Aaron W. James,

    1. Dental and Craniofacial Research Institute and Section of Orthodontics, School of Dentistry, University of California, Los Angeles, Los Angeles, California 90095
    2. UCLA and Orthopaedic Hospital, Department of Orthopaedic Surgery and the Orthopaedic Hospital Research Center, University of California, Los Angeles, Los Angeles, California 90095
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  • Jonguk Chung,

    1. Dental and Craniofacial Research Institute and Section of Orthodontics, School of Dentistry, University of California, Los Angeles, Los Angeles, California 90095
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  • Kiho Lee,

    1. Dental and Craniofacial Research Institute and Section of Orthodontics, School of Dentistry, University of California, Los Angeles, Los Angeles, California 90095
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  • James B. Zhang,

    1. Dental and Craniofacial Research Institute and Section of Orthodontics, School of Dentistry, University of California, Los Angeles, Los Angeles, California 90095
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  • Stephanie Ho,

    1. Dental and Craniofacial Research Institute and Section of Orthodontics, School of Dentistry, University of California, Los Angeles, Los Angeles, California 90095
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  • Kevin S. Lee,

    1. Dental and Craniofacial Research Institute and Section of Orthodontics, School of Dentistry, University of California, Los Angeles, Los Angeles, California 90095
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  • Toyong M. Kim,

    1. Dental and Craniofacial Research Institute and Section of Orthodontics, School of Dentistry, University of California, Los Angeles, Los Angeles, California 90095
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  • Tomoaki Niimi,

    1. Department of Bioengineering Sciences, Graduate School of Bioagricultural Sciences, Nagoya University, Furocho, Chikusa-ku, Nagoya 464-8601, Japan
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  • Shun'ichi Kuroda,

    1. Department of Bioengineering Sciences, Graduate School of Bioagricultural Sciences, Nagoya University, Furocho, Chikusa-ku, Nagoya 464-8601, Japan
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  • Kang Ting,

    Corresponding author
    1. Dental and Craniofacial Research Institute and Section of Orthodontics, School of Dentistry, University of California, Los Angeles, Los Angeles, California 90095
    2. UCLA and Orthopaedic Hospital, Department of Orthopaedic Surgery and the Orthopaedic Hospital Research Center, University of California, Los Angeles, Los Angeles, California 90095
    • School of Dentistry, University of California, Box 951668, CHS 30-113, Los Angeles, CA 90095-1668.
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  • Chia Soo

    Corresponding author
    1. UCLA and Orthopaedic Hospital, Department of Orthopaedic Surgery and the Orthopaedic Hospital Research Center, University of California, Los Angeles, Los Angeles, California 90095
    • 200 UCLA Medical Plaza Suite 445, Los Angeles, California 90095.
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  • Disclosures: Drs. K.T. and C.S. are inventors of Nell-1 related patents. Drs. K.T. and C.S. are founders of Bone Biologics, Inc., which sublicenses Nell-1 patents from the UC Regents.

Abstract

NELL-1 (Nel-like molecule-1) is a secreted osteogenic growth factor first identified in human craniosynostosis (CS) patients. NELL-1 protein has been observed to promote bone and cartilage differentiation and to suppress adipogenesis in both in vitro and in vivo models. Despite these findings, the cell surface receptors of NELL-1 have remained unknown. In this study, we observed for the first time that NELL-1 promotes cell adherence in multiple cell lines, including ST2, C3H10T1/2, M2-10B4, ATDC5, and MC3T3 cells. Additionally, we found that NELL-1 binds to extracellular Integrinβ1 and induces cell focal adhesion. By utilizing siRNA methods, we determined that NELL-1 cell surface binding and enhanced cell attachment were dependent on Integrinβ1 expression. Finally, we observed that pre-coating of culture dishes or PLGA (polylactic-co-glycolic acid) scaffold with NELL-1 resulted in a significant increase in both cell attachment and osteogenic differentiation. Our results identify for the first time a cell surface target of NELL-1, Integrinβ1, and elucidate new functions of NELL-1 in promoting cell adherence and osteogenic differentiation. J. Cell. Biochem. 113: 3620–3628, 2012. © 2012 Wiley Periodicals, Inc.

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