Expression and effects of glial cell line-derived neurotrophic factor on periodontal ligament cells

J Clin Periodontol. 2012 Jun;39(6):556-64. doi: 10.1111/j.1600-051X.2012.01881.x. Epub 2012 Apr 18.

Abstract

Aim: To investigate Glial cell line-derived neurotrophic factor (GDNF) expression in normal and wounded rat periodontal ligament (PDL) and the effects of GDNF on human PDL cells (HPDLCs) migration and extracellular matrix expression in HPDLCs.

Material and methods: The expression of GDNF and GDNF receptors was examined by immunocyto/histochemical analyses. Gene expression in HPDLCs treated with GDNF, interleukin-1 beta (IL-1β), or tumour necrosis factor-alpha (TNF-α) was quantified by quantitative RT-PCR (qRT-PCR). In addition, we examined the migratory effect of GDNF on HPDLCs.

Results: GDNF was expressed in normal rat PDL and cultured HPDLCs. HPDLCs also expressed GDNF receptors. In wounded rat PDL, GDNF expression was up-regulated. QRT-PCR analysis revealed that IL-1β and TNF-α significantly increased the expression of GDNF in HPDLCs. Furthermore, GDNF induced migration of HPDLCs, which was blocked by pre-treatment with the peptide including Arg-Gly-Asp (RGD) sequence, or neutralizing antibodies against integrin αVβ3 or GDNF. Also, GDNF up-regulated expression of bone sialoprotein (BSP) and fibronectin in HPDLCs.

Conclusions: GDNF expression is increased in rat wounded PDL tissue and HPDLCs treated with pro-inflammatory cytokines. GDNF enhances the expression of BSP and fibronectin, and migration in an RGD-dependent manner via the integrin αVβ3. These findings suggest that GDNF may contribute to wound healing in PDL tissue.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alveolar Bone Loss / metabolism*
  • Animals
  • Cell Adhesion
  • Cell Movement / drug effects
  • Cells, Cultured
  • Extracellular Matrix Proteins / biosynthesis*
  • Extracellular Matrix Proteins / genetics
  • Female
  • Fibronectins / biosynthesis
  • Fibronectins / genetics
  • Gene Expression Regulation
  • Glial Cell Line-Derived Neurotrophic Factor / genetics
  • Glial Cell Line-Derived Neurotrophic Factor / metabolism*
  • Glial Cell Line-Derived Neurotrophic Factor / pharmacology
  • Glial Cell Line-Derived Neurotrophic Factor Receptors / metabolism
  • Humans
  • Integrin-Binding Sialoprotein / biosynthesis
  • Integrin-Binding Sialoprotein / genetics
  • Interleukin-1beta / pharmacology
  • Male
  • Oligopeptides / metabolism
  • Periodontal Ligament / cytology
  • Periodontal Ligament / drug effects*
  • Periodontal Ligament / metabolism*
  • Periodontal Ligament / pathology
  • Platelet Glycoprotein GPIIb-IIIa Complex / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Recombinant Proteins / pharmacology
  • Tumor Necrosis Factor-alpha / pharmacology
  • Wound Healing / physiology
  • Young Adult

Substances

  • Extracellular Matrix Proteins
  • Fibronectins
  • Glial Cell Line-Derived Neurotrophic Factor
  • Glial Cell Line-Derived Neurotrophic Factor Receptors
  • Integrin-Binding Sialoprotein
  • Interleukin-1beta
  • Oligopeptides
  • Platelet Glycoprotein GPIIb-IIIa Complex
  • Recombinant Proteins
  • Tumor Necrosis Factor-alpha
  • arginyl-glycyl-aspartic acid