Recent studies have showed that psychosocial stress causes elevated secretion of cortisol, the principal glucocorticoid (GC), and thus increases the extent of periodontal breakdown. In this study, we investigated whether stress-associated periodontal disturbance may be due to GC-induced changes in the periodontal ligament stem cells (PDLSCs), one of the most promising candidates for periodontal tissue regeneration. Our results in this study showed that dexamethasone (Dex) treatment causes the translocation of the glucocorticoid receptor (GR) into the nucleus and increases the expression of many genes, including dickkopf-1 (DKK-1) in PDLSCs. ELISA showed that DKK-1 is secreted from PDLSCs in response to Dex treatment. The GR antagonist RU486 attenuated the Dex-inducible DKK-1 messenger RNA (mRNA) expression. DKK-1 inhibited the growth of PDLSCs and suppressed Wnt-mediated activation of β-catenin signaling in PDLSCs. Our results strongly suggest that stress-associated periodontal disturbance may be due to GC-induced changes in the activity of PDLSCs via DKK-1 expression and might provide a possible explanation for the deteriorating effect of stress on periodontal breakdown.

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