PlexinA2 mediates osteoblast differentiation via regulation of Runx2

Authors

  • Ji-Eun Oh,

    1. Department of Cell and Developmental Biology, BK21 and DRI, Seoul National University School of Dentistry, Seoul, Korea
    2. Department of Biomedical Laboratory Science, Far East University, Chungbuk, Korea
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    • These authors contributed equally to this work and share first authorship.

  • Hyung Joon Kim,

    1. Department of Cell and Developmental Biology, BK21 and DRI, Seoul National University School of Dentistry, Seoul, Korea
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    • These authors contributed equally to this work and share first authorship.

  • Woo-Shin Kim,

    1. Department of Cell and Developmental Biology, BK21 and DRI, Seoul National University School of Dentistry, Seoul, Korea
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  • Zang Hee Lee,

    1. Department of Cell and Developmental Biology, BK21 and DRI, Seoul National University School of Dentistry, Seoul, Korea
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  • Hyun-Mo Ryoo,

    1. Department of Molecular Genetics, BK21 and DRI, Seoul National University School of Dentistry, Seoul, Korea
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  • Soon Jung Hwang,

    1. Department of Oral and Maxillofacial Surgery, Seoul National University School of Dentistry, Seoul, Korea
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  • Youngkyun Lee,

    1. Department of Cell and Developmental Biology, BK21 and DRI, Seoul National University School of Dentistry, Seoul, Korea
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  • Hong-Hee Kim

    Corresponding author
    1. Department of Cell and Developmental Biology, BK21 and DRI, Seoul National University School of Dentistry, Seoul, Korea
    • Department of Cell and Developmental Biology, Seoul National University, 28 Yeongon-dong, Chongno-Gu, Seoul 110-749, Korea.
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Abstract

The imbalance between bone-resorbing osteoclasts and bone-forming osteoblasts often leads to bone destructive diseases such as osteoporosis. In contrast to the development of several antiresorptive agents for osteoporosis therapy, discovery of anabolic drugs has been difficult because of an insufficient understanding of the complex mechanism of bone formation. In a microarray analysis with mouse preosteoblast cells, we found that PlexinA2 (PlxnA2), a molecule previously known to mediate axon guidance in neural development, was upregulated by the osteogenic factor BMP2. PlxnA2-specific siRNA decreased Runx2 expression, osteoblast differentiation, and mineralization. Runx2 overexpression restored osteoblastic differentiation of PlxnA2-knockdown cells. PlxnA2 was associated with both type 1 and 2 BMP receptors, and BMP2 increased the interaction between PlxnA2 and type 1 receptors. PlxnA2 also affected Smad and Akt signaling pathways downstream of BMP2. Taken together, the results of our study reveal that PlxnA2 has a pro-osteogenic function by modulating BMP2 signaling. Therefore, PlxnA2 may be a useful target for development of bone anabolic therapeutics. © 2012 American Society for Bone and Mineral Research

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