Oral Biology, School of Dentistry, College of Medical and Dental Sciences, St Chad's Queensway, University of Birmingham, Birmingham BR 6NN, UK.
J Dent Res. 2011 Oct;90(10):1240-5. doi: 10.1177/0022034511417443. Epub 2011 Aug 9.
This study investigated the effects of glial cell line-derived neurotrophic factor (GDNF) on dental pulp 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, GDNF dose-dependently increased viable cell number under serum-free culture conditions. Live/dead, lactate dehydrogenase (LDH), and caspases-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 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 cytoprotective under disease conditions. In conclusion, our findings indicate that GDNF promotes cell survival and proliferation of DPCs and suggest that GDNF may play a multifunctional role in the regulation of dental pulp homeostasis.
本研究探讨了胶质细胞源性神经营养因子（GDNF）对牙髓细胞（DPCs）的影响。DPCs 的培养物表达 GDNF 及其受体 GFRα1 和 RET。在含血清的培养基中添加重组 GDNF 对 DPC 生长没有显著影响；然而，GDNF 在无血清培养条件下呈剂量依赖性增加活细胞数量。台盼蓝/碘化丙啶（Live/Dead）、乳酸脱氢酶（LDH）和半胱天冬酶-3/-7 测定表明，在无血清条件下发生细胞死亡，GDNF 通过抑制细胞凋亡死亡显著减少死亡细胞数量。通过 BrdU 掺入测定评估，GDNF 还刺激无血清条件下的细胞增殖。在存在 GFRα1 和 RET 抑制剂的情况下，GDNF 的作用被消除，提示受体介导的事件。本研究还表明，GDNF 可拮抗 TNFα 诱导的 DPC 细胞毒性，提示 GDNF 在疾病条件下可能具有细胞保护作用。总之，我们的研究结果表明，GDNF 促进 DPCs 的细胞存活和增殖，并提示 GDNF 可能在牙髓内稳态的调节中发挥多种功能。
