Possible involvement of extracellular signal‐regulated kinases 1/2 in mitogenic response of periodontal ligament cells to enamel matrix derivative

The efficacy of enamel matrix derivative (EMD) as an adjunct to periodontal regenerative therapy has been demonstrated in recent clinical studies, however, little is known about its molecular mechanism (s). We examined the mitogenic response of cultured periodontal ligament (PDL) cells to EMD and characterized associated changes in proliferation-related intracellular signaling molecules, including mitogen-activated protein kinases (MAPK) and Akt kinases/protein kinase B (Akt/PKB) kinases. The DNA synthesis of PDL cells increased following treatment with EMD at concentrations higher than 1 microg ml(-1). This mitogenic response to EMD was associated with the selective activation of extracellular signal-regulated kinase (ERK) 1/2. No other MAPKs, or Akt/PKB kinases, responded to EMD stimulation. The EMD induction of DNA synthesis and activation of ERK 1/2 were diminished by pretreatment with suramin, an inhibitor of receptor tyrosine kinases (RTK). The signaling pathway induced by EMD from RTK to ERK 1/2 was similar to that activated by epidermal growth factor (EGF), although the specific binding of 125I-EGF to PDL cells was not affected by pretreatment or concomitant treatment with EMD. These findings suggest that EMD elicits its mitogenic signal through an EMD-specific RTK towards ERK 1/2.