Cyclic stretching force induces apoptosis in human periodontal ligament cells via caspase-9

The response of periodontal ligament (PDL) cells to mechanical stimulation is important in the periodontal tissue remodelling. Our previous study showed that cyclic stretching force on PDL cells induced early apoptosis. However, the mechanism of stretching force-induced cell death is unclear. In the present study, we examined whether PDL cells undergo apoptosis by stretching force using the terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick-end-labellling method (TUNEL) and investigated the mechanism by which cyclic stretching force initiated apoptosis. We found that PDL cells became aligned regularly and the number of apoptotic cells increased significantly in a time-and force-dependent manner after the application of cyclic stretching force. Caspase-3 activity increased in proportion to the magnitude of the stretching force, and this effect was reduced significantly by a caspase-9 inhibitor, whereas a caspase-8 inhibitor had no such effect. We therefore concluded that the in vitro application of cyclic stretching force can induce apoptosis in PDL cells by activating the caspase-3 via the caspase-9 signalling cascade. Our findings may provide a novel insight into the mechanism of apoptosis induced by stretching force in PDL cells.