BDNF Regulates p75-JNK Signaling Cascade to Induce Gingival Epithelial Cells Apoptosis

Objectives: Brain-derived neurotrophic factor (BDNF) is known to play a role in proliferation and differentiation in various types of cells. Previously, we have reported that BDNF enhances periodontal tissue regeneration in dog periodontal defect model. Importantly, the down growth of gingival epithelium which comprises a major obstacle to the regeneration was not observed. For the clinical application of BDNF, it is indispensable to reveal the molecular mechanism underlying this key finding. On the other hands, it is reported that BDNF induces neuronal cells apoptosis via p75-JNK signaling. Therefore, the aim of this study is to test whether BDNF facilitates apoptosis via p75-JNK cascade of human gingival epithelial cells.
Methods: Immortalized human gingival epithelial cells (OBA9) and immortalized human periodontal ligament cells (HPL cells) were employed. The cells were exposed to BDNF. The cell proliferation and apoptosis was determined by BrdU assay and TUNEL staining, respectively. In addition, phosphorylation of ERK, JNK and cleaved-caspase3 were detected by immunoblotting. Furthermore, an inhibition assay was conducted by using JNK inhibitor, SP600125 or p75 siRNA transfection.


Results: BDNF treatment facilitated cell proliferation and phosphorylation of ERK in HPL cells. However, contrary to HPL cells, OBA9 showed neither cell proliferation nor phosphorylation of ERK but demonstrated cell apoptosis by BDNF stimulation. BDNF increased cleaved-caspase3 and phosphorylation of JNK expression in OBA9 and these elevations were clearly diminished by JNK and p75 siRNA transfection.
Conclusions: These findings suggested that BDNF can activate p75-JNK-caspase3 signaling cascade in human gingival epithelial cells to induce cell apoptosis.