Direct effect of streptozotocin on periodontal ligament cells through myeloid cell leukemia-1

Objective: We hypothesized that streptozotocin (STZ) has a direct impact on periodontal ligament cell (PDL) damage as a potential direct inducer of periodontitis. Background: Since diabetes was accepted as one of the risk factors for the development of periodontal disease, various scientific studies have been undertaken in the STZ-induced periodontal disease models. STZ induces β-cell damage and subsequent diabetes development in vivo. Until now, assessment of the impacts of STZ-induced experimental diabetes on periodontitis has generally been conducted on the fundamental assumption that STZ have no direct action on PDL and its function. However, several recent studies suggest that STZ also directly affect many different biological functions in various tissues or organs. Material and Methods: To assess the apoptotic effects of STZ on PDLs, they were treated with or without STZ at different concentrations. Qualitative estimation of apoptotic cell death was obtained by live/dead assay. The expression levels of apoptosis-related proteins were evaluated by western blot analysis. Results: STZ inhibits growth and induces apoptosis in PDLs in a dose-dependent manner. Furthermore, STZ dramatically induced Mcl-1 downregulation in a proteasome-dependent manner and thereby induced apoptosis of PDLs through the Bak/Bax apoptotic signaling pathway. Conclusion: Our results support the hypothesis that suppression of the cellular Mcl-1 levels by STZ may be at least partly attributed to the development of periodontitis in STZ-induced diabetic animal models.