Effects of glial cell line-derived neurotrophic factor on dental pulp cells

This study investigated the effects of glial cell line-derived neurotrophic factor (GDNF) on dental pulp stromal cells (DPCs). Cultures of DPCs expressed GDNF as well as its receptors, GFRα1 and RET. Addition of recombinant GDNF to cultures in serum-containing medium did not significantly affect DPC growth; however, GNDF dose-dependently increased viable cell number under serum-free culture conditions. Live/dead, lactate dehydrogenase (LDH) and caspase -3,-7 assays demonstrated that cell death occurred under serum-free conditions, and that GDNF significantly reduced the number of dead cells by inhibiting apoptotic cell death. GDNF also stimulated cell proliferation in serum-free conditions, as assessed by the BrdU incorporation assay. The effect of GDNF was abolished in the presence of specific inhibitors to GFRα1 and RET suggesting receptor-mediated events. This study also demonstrated that GDNF counteracted TNFα-induced DPC cytotoxicity, suggesting that GDNF may be cytoptotective under disease conditions. In conclusion, our findings indicate that GDNF promotes cell survival and proliferation of DPC and suggest that GDNF may play a multi-functional role in the regulation of dental pulp homeostasis.