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Glial cell line-derived neurotrophic factor influences proliferation of osteoblastic cells

Gale, Z. and Cooper, P. R. and Scheven, B. A. A. (2012) Glial cell line-derived neurotrophic factor influences proliferation of osteoblastic cells. Cytokine, 57 (2). pp. 276-281. ISSN 10434666

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URL of Published Version: http://dx.doi.org/10.1016/j.cyto.2011.10.023

Identification Number/DOI: 10.1016/j.cyto.2011.10.023

Little is known about the role of neurotrophic growth factors in bone metabolism. This study investigated the short-term effects of glial cell line-derived neurotrophic factor (GDNF) on calvarial-derived MC3T3-E1 osteoblasts. MC3T3-E1 expressed GDNF as well as its canonical receptors, GFRα1 and RET. Addition of recombinant GDNF to cultures in serum-containing medium modestly inhibited cell growth at high concentrations; however, under serum-free culture conditions GDNF dose-dependently increased cell proliferation. GDNF effects on cell growth were inversely correlated with its effect on alkaline phosphatase (ALP) activity showing a significant dose-dependent inhibition of relative ALP activity with increasing concentrations of GDNF in serum-free culture medium. Live/dead and lactate dehydrogenase assays demonstrated GDNF did not significantly affect cell death or survival under serum-containing and serum-free conditions. The effect of GDNF on cell growth was abolished in the presence of inhibitors to GFR α 1 and RET indicating that GDNF stimulated calvarial osteoblasts via its canonical receptors. Finally, this study found that GDNF synergistically increased tumor necrosis factor-α (TNF-α)-stimulated MC3T3-E1 cell growth suggesting that GDNF interacted with TNF-α-induced signaling in osteoblastic cells. In conclusion, this study provides evidence for a direct, receptor-mediated effect of GDNF on osteoblasts highlighting a novel role for GDNF in bone physiology.

Type of Work:Article
Date:February 2012 (Publication)
School/Faculty:Colleges (2008 onwards) > College of Medical & Dental Sciences
Department:School of Dentistry
Keywords:GDNF, neurotrophic factor, TNF-alpha, osteoblast, bone, calvarial, cell proliferation
Subjects:RK Dentistry
Institution:University of Birmingham
Copyright Holders:Elsevier, The authors
ID Code:1141
Refereed:YES
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