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周期性牵张力通过半胱天冬氨酸蛋白酶-9诱导人牙周膜细胞凋亡。

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

机构信息

Department of Prosthodontics, Ninth People's Hospital, School of Stomatology, Shanghai JiaoTong University School of Medicine, Shanghai, China.

出版信息

Arch Oral Biol. 2009 Sep;54(9):864-70. doi: 10.1016/j.archoralbio.2009.05.012. Epub 2009 Jun 27.

Abstract

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.

摘要

牙周膜(PDL)细胞对机械刺激的反应在牙周组织重塑中很重要。我们之前的研究表明,周期性拉伸力可诱导牙周膜细胞早期凋亡。然而,拉伸力诱导细胞死亡的机制尚不清楚。在本研究中,我们使用末端脱氧核苷酸转移酶(TdT)介导的 dUTP-生物素缺口末端标记法(TUNEL)检测了 PDL 细胞是否通过拉伸力发生凋亡,并探讨了周期性拉伸力引发凋亡的机制。结果发现,PDL 细胞在周期性拉伸力作用下呈现出规则排列,细胞凋亡数量随时间和力的增加而显著增加。半胱天冬酶-3 的活性与拉伸力的大小成比例增加,而半胱天冬酶-9 的抑制剂可显著降低这种作用,而半胱天冬酶-8 的抑制剂则没有这种作用。因此,我们得出结论,体外应用周期性拉伸力可通过 caspase-9 信号级联激活半胱天冬酶-3 诱导 PDL 细胞凋亡。我们的发现可能为拉伸力诱导 PDL 细胞凋亡的机制提供新的见解。

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