Glial cell line-derived neurotrophic factor effects on dental pulp cells and osteoblast-like cells

Abstract

Glial cell line-derived neurotrophic factor (GDNF) is a growth factor promoting survival, proliferation and differentiation of neural crest cells. Neural crest cells play an important role within mesenchymal tissues during dental pulp and calvarial bone development. GDNF also has a role within non-neuronal tissues and is expressed during dental development. GDNF null mutations prevent the formation of the mineralised hard tissues of the tooth. The hypothesis for this study was that GDNF affects mesenchymal dental pulp cells (DPC), promoting the regenerative responses of mineralised tissues. This study utilised cell culture models to investigate the direct effects of GDNF on the proliferation and differentiation of dental pulp cells, bone marrow mesenchymal stromal/stem cells (BMSC) and calvarial osteoblasts. This research demonstrated that these culture models expressed GDNF and its receptors GFR\(\alpha\)1 and RET. GDNF was shown to directly stimulate DPC and osteoblast-like cell proliferation and differentiation. Moreover, GDNF was cytoprotective when DPCs were cultured under conditions reflecting aspects of inflammation, which may occur during repair. These conditions included supplementation with the pro-inflammatory cytokine TNF\(\alpha\) and culture under serum-starved conditions. It is proposed that GDNF may play an important regulatory role in dental pulp homeostasis and bone metabolism.