Brain-derived neurotrophic factor protects cementoblasts from serum starvation-induced cell death
Article first published online: 26 AUG 2009
Copyright © 2009 Wiley-Liss, Inc.
Journal of Cellular Physiology
Volume 221, Issue 3, pages 696–706, December 2009
How to Cite
Kajiya, M., Shiba, H., Fujita, T., Takeda, K., Uchida, Y., Kawaguchi, H., Kitagawa, M., Takata, T. and Kurihara, H. (2009), Brain-derived neurotrophic factor protects cementoblasts from serum starvation-induced cell death. J. Cell. Physiol., 221: 696–706. doi: 10.1002/jcp.21909
- Issue published online: 25 SEP 2009
- Article first published online: 26 AUG 2009
- Manuscript Accepted: 17 JUL 2009
- Manuscript Received: 31 MAR 2009
- Japan Society for the Promotion of Science, Japan. Grant Number: 18390560
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.