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Mediation of Rac1 activation by kindlin-2: An essential function in osteoblast adhesion, spreading, and proliferation

Authors

  • Gil-Yong Jung,

    1. Interdisciplinary Program for Bioengineering, Seoul National University, Seoul 152-742, Korea
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  • Yoon-Jeong Park,

    1. Interdisciplinary Program for Bioengineering, Seoul National University, Seoul 152-742, Korea
    2. Department of Craniomaxilofacial Reconstructive Science, School of Dentistry, Seoul 110-749, Korea
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  • Jung-Suk Han

    Corresponding author
    1. Department of Prosthodontics and Dental Research Center, School of Dentistry, Seoul National University, Seoul 110-749, Korea
    • Department of Prosthodontics and Dental Research Center, School of Dentistry, Seoul National University, Seoul 110-749, Republic of Korea.
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Abstract

Kindlins are focal adhesion proteins that regulate integrin signaling. Although integrin activation is critical for bone development, little is known about the expression and role of kindlins in osteoblasts. We therefore investigated the function of kindlin-2 in osteoblast adhesion, spreading, and proliferation using small interfering RNA. In MC3T3-E1 cells, only kindlin-2 is highly expressed and localizes to focal adhesion. We found that kindlin-2 was involved in integrin activation in MC3T3-E1 cells and that kindlin-2 knockdown osteoblasts resulted in diminished cell adhesion, spreading, and proliferation. In this process, kindlin-2 knockdown impaired transient Rac1 activation, influencing Akt activation and AP-1 activity. In agreement with these data, pharmacological inhibition of Rac1 reduced MC3T3-E1 cell adhesion, spreading, and proliferation. Overall, these findings demonstrated that kindlin-2 governs Rac1 activation, which controls osteoblast function. Our findings provide the first insights concerning the function of kindlin-2 in osteoblast, and suggest that kindlin-2 is a critical mediator for osteoblast physiology. J. Cell. Biochem. 112: 2541–2548, 2011. © 2011 Wiley-Liss, Inc.

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