High Levels of Glucose Induced the Caspase-3/PARP Signaling Pathway, Leading to Apoptosis in Human Periodontal Ligament Fibroblasts

Abstract

Periodontitis is one of the main complications of diabetes mellitus, and much research has been conducted on their relationship. However, the mechanism by which high glucose levels induce damage of periodontal ligament fibroblasts is still unclear. In this study, we investigated the effects of high glucose levels on apoptosis in human periodontal ligament fibroblasts and the possible mechanisms involved. Human periodontal ligament fibroblasts were cultured in DMEM with normal glucose (5.5 mM) and high glucose (35 mM) levels for 6, 12, or 24 h. Apoptosis was studied by flow cytometry, caspase assays, fluorescent real-time PCR, and Western-blot analysis. The different durations of high glucose incubation induced a time-dependent increase of apoptosis and caspase-3 activity in cultured human periodontal ligament fibroblasts. In addition, concentrations of caspase-3 and its substrate PARP in cultured human periodontal ligament fibroblasts increased in a time-dependent manner. Furthermore, a caspase-3 inhibitor could prevent the high glucose-induced apoptosis in human periodontal ligament fibroblasts. These data indicate that high glucose induces a time- and caspase-3-dependent increase in apoptosis in cultured human periodontal ligament fibroblasts. These results elucidate the mechanism for the regulation of human periodontal ligament fibroblast apoptosis caused by high glucose.