Effect of HB-EGF on Wound-Healing in PDL

Objective: There is growing attention on periodontal regeneration and wound healing for periodontal therapy and replantation of avulsed tooth. This study is to investigate the effects of heparin-binding epidermal growth factor-like growth factor (HB-EGF) on cell repopulation and signal transduction in periodontal ligament (PDL) cell after scratch-wounding in vitro.

Methods: Human PDL cells were obtained from the explant tissue of human healthy PDL. After wounding PDL cells, the change of mRNA expression of HB-EGF and epidermal growth factor receptor (EGFR) 1 to 4 was examined. The effects of HB-EGF on the PDL cell proliferation and repopulation were examined in vitro by MTT assay and photographing of injury, respectively. The phosphorylation of Erk1/2, p38 and Akt was determined by Western blot analysis.

Results: Scratch-wound upregulated significantly mRNA expression of HB-EGF whereas the wound didn't change the expression levels of EGFR1 to 4. Interestingly, the expression of EGFR2 and 4 was not detectable before and after the wounding. Treatment of HB-EGF promoted PDL cell proliferation and repopulation. The scratch-wound stimulated phosphorylation of Erk1/2 and p38 but not Akt in PDL cells, and the treatment of HB-EGF after the wounding amplified the activations of Erk1/2 and p38 but not Akt. Furthermore, the inhibition of Erk1/2 blocked the process of cell repopulation induced by HB-EGF while the inhibition of p38 delayed the process.

Conclusion: These results suggest that HB-EGF may be a critical factor in wound healing of human PDL cells by a mechanism that requires Erk1/2 activation via the specific interaction with EGFR1.

This work was supported by the Korea Research Foundation Grant (KRF-2007-E00512).