Brain-derived neurotrophic factor protects cementoblasts from serum starvation-induced cell death

Authors

  • Mikihito Kajiya,

    1. Department of Periodontal Medicine, Hiroshima University Graduate School of Biomedical Sciences, Minami-ku, Hiroshima, Japan
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  • Hideki Shiba,

    Corresponding author
    1. Department of Periodontal Medicine, Hiroshima University Graduate School of Biomedical Sciences, Minami-ku, Hiroshima, Japan
    • Department of Periodontal Medicine, Division of Frontier Medical Science, Hiroshima University Graduate School of Biomedical Sciences, 1-2-3, Kasumi, Minami-ku, Hiroshima 734-8553, Japan.
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  • Tsuyoshi Fujita,

    1. Department of Periodontal Medicine, Hiroshima University Graduate School of Biomedical Sciences, Minami-ku, Hiroshima, Japan
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  • Katsuhiro Takeda,

    1. Department of Periodontal Medicine, Hiroshima University Graduate School of Biomedical Sciences, Minami-ku, Hiroshima, Japan
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  • Yuushi Uchida,

    1. Department of Periodontal Medicine, Hiroshima University Graduate School of Biomedical Sciences, Minami-ku, Hiroshima, Japan
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  • Hiroyuki Kawaguchi,

    1. Department of Periodontal Medicine, Hiroshima University Graduate School of Biomedical Sciences, Minami-ku, Hiroshima, Japan
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  • Masae Kitagawa,

    1. Center of Oral Clinical Examination, Hiroshima University Hospital, Minami-ku, Hiroshima, Japan
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  • Takashi Takata,

    1. Department of Oral and Maxillofacial Pathobiology, Hiroshima University Graduate School of Biomedical Sciences, Minami-ku, Hiroshima, Japan
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  • Hidemi Kurihara

    1. Department of Periodontal Medicine, Hiroshima University Graduate School of Biomedical Sciences, Minami-ku, Hiroshima, Japan
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Abstract

Our previous studies have shown that brain-derived neurotrophic factor (BDNF) enhances bone/cementum-related protein gene expression through the TrkB-c-Raf-ERK1/2-Elk-1 signaling pathway in cementoblasts, which play a critical role in the establishment of a functional periodontal ligament. To clarify how BDNF regulates survival in cementoblasts, we examined its effects on cell death induced by serum starvation in immortalized human cementoblast-like (HCEM) cells. BDNF inhibited the death of HCEM cells. Small-interfering RNA (siRNA) for TRKB, a high affinity receptor for BDNF, and for Bcl-2, countered the BDNF-induced decrease in dead cell number. In addition, LY294002, a PI3-kinase inhibitor; SH-6, an Akt inhibitor; and PDTC, a nuclear factor kappa B (NF-κB) inhibitor, but not PD98059, an ERK1/2 inhibitor, abolished the protective effect of BDNF against cell death. BDNF enhanced phosphorylated Akt levels, NF-κB activity in the nucleus, Bcl-2 mRNA levels, and mitochondrial membrane potential. The blocking of BDNF's actions by treatment with siRNA in all cases for TRKB and Bcl-2, LY294002, SH-6, and PDTC suppressed the enhancement. These findings provide the first evidence that a TrkB-PI3-kinase-Akt-NF-κB-Bcl-2 signaling pathway triggered by BDNF and the subsequent protective effect of BDNF on mitochondrial membrane potential are required to rescue HCEM cells from serum starvation-induced cell death. Furthermore, the survival and increased expression of bone/cementum-related proteins induced by BDNF in HCEM cells occur through different signaling pathways. J. Cell. Physiol. 221: 696–706, 2009. © 2009 Wiley-Liss, Inc.

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