The mechanism of fluoride-induced apoptosis of ameloblasts mediated by KLK4
- VernacularTitle:KLK4介导氟诱发成釉细胞凋亡的作用机制
- Author:
Xiaojing LIU
1
;
Meili GAO
2
;
Jianping RUAN
3
,
4
Author Information
- Publication Type:Journal Article
- Keywords: ameloblast; fluoride; kallikrein-4 (KLK4); cell proliferation; cell cycle; cell apoptosis
- From: Journal of Xi'an Jiaotong University(Medical Sciences) 2024;45(6):918-926
- CountryChina
- Language:Chinese
- Abstract: [Objective] To investigate the effects of fluoride on kallikrein-4 (KLK4) and cell apoptosis as well as the possible mechanisms in ALC cells. [Methods] ALC cells were treated with different concentrations of fluoride for 24 and 48 hours. The effects on cell viability, cell cycle and cell apoptosis were detected using CCK-8, flow cytometry and hoechst 33342, respectively. KLK4 expression was detected by qRT-PCR and Western blotting, and the protein expressions of glucose-regulated protein 78 (GRP78), p-eukaryotic initiation factor 2α (eIF2α), activating transcription factor 4 (ATF4), and C/EBP homologous protein (CHOP) were detected by Western blotting. [Results] The results showed that the expression of KLK4 was significantly reduced after treatment with 1.0 and 2.0 mmol/L NaF for 24 and 48 hours (P<0.05). The difference was statistically significant in cell activity between 2.0 mmol/L NaF treatment group and the control group (P<0.05). The G0/G1 phase cells significantly reduced and the S phase cells significantly increased after treatment with 0.1 and 1.0 mmol/L NaF for 24 hours (P<0.05), while the G0/G1 phase cells significantly increased and the S phase cells significantly reduced in the 2.0 mmol/L NaF treatment cells (P<0.05). The G0/G1 phase cells significantly increased and G2/M phase cells significantly reduced after treatment with 2.0 mmol/L NaF for 48 hours (P<0.05). With the increase of NaF treatment concentration, the number of bright blue cells gradually increased, and the percentage of apoptosis also increased successively. Except for the cells treated with 0.1 mmol/L NaF for 24 hours, the apoptosis rate of the other fluoride treatment groups was statistically significant compared with the control group (P<0.05). The expressions of GRP78 and p-eIF2α were significantly increased after treatment with 0.1, 1.0, and 2.0 mmol/L NaF for 24 hours (P<0.05). The expressions of ATF4 and CHOP were significantly increased after treatment with 1.0 and 2.0 mmol/L NaF for 24 hours (P<0.05). The expressions of ATF4 and CHOP were significantly increased after treatment with 0.1, 1.0, and 2.0 mmol/L NaF for 48 hours (P<0.05). [Conclusion] Sodium fluoride may result in inhibition of KLK4 expression and abnormal cell growth, possibly by inducing GRP78 expression and activating eIF2α/ATF4/CHOP signaling pathway in ALC ameloblasts.
