Effects of chronic fluorosis on the expression of VEGF/PI3K/AKT/eNOS in the gingival tissue of rats with orthodontic tooth movement

Ding,Xue; Lai,Lingyan; Jia,Ying; Liu,Xingyun; Hu,Jia; Chen,Wanlin

doi:10.3892/etm.2024.12409

Effects of chronic fluorosis on the expression of VEGF/PI3K/AKT/eNOS in the gingival tissue of rats with orthodontic tooth movement

Authors:
- Xue Ding
- Lingyan Lai
- Ying Jia
- Xingyun Liu
- Jia Hu
- Wanlin Chen
View Affiliations

Affiliations: Department of Stomatology, Guizhou Provincial People's Hospital, Guiyang, Guizhou 550002, P.R. China, Department of Orthodontics, School of Stomatology, Guizhou Medical University, Guiyang, Guizhou 550004, P.R. China
Published online on: January 31, 2024 https://doi.org/10.3892/etm.2024.12409
Article Number: 121
Copyright: © Ding et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

It has been reported that the force of orthodontic correction triggers periodontal tissue remodeling by affecting angiogenesis. However, the manifestation of the vascular response to orthodontic tooth movement in the setting of chronic fluorosis is unclear. The aim of the present study was to preliminarily explore the effect of orthodontic treatment on the angiogenesis of gingival tissue in rats with chronic fluorosis by monitoring changes in the expression of vascular endothelial growth factor (VEGF), phosphatidylinositol‑3 kinase (PI3K), AKT (or protein kinase B) and endothelial nitric oxide synthase (eNOS) in the gingival tissue. A total of 60 rats were randomly divided equally into the orthodontic group (O group; n=30) and fluorosis orthodontic group (FO group; n=30). Each of these groups was divided into 0‑, 3‑, 7‑, 14‑ and 21‑day groups (n=6/group). Fluorosis and orthodontic tooth movement models were established, and rats in each group were sacrificed for tissue sampling at the corresponding time points. Tissue morphology was observed via hematoxylin and eosin (H&E) staining. The protein and mRNA expression levels of VEGF, PI3K, AKT and eNOS in gingival tissue were detected by western blotting and reverse transcription‑quantitative polymerase chain reaction, respectively. The H&E staining images showed that the FO group had smaller blood vessels and reduced vascular proliferation compared with the O group. Furthermore, the mRNA and protein expression levels of VEGF, PI3K, AKT and eNOS were reduced in the gingiva of rats in the FO group compared with the O group, and certain reductions were significant during the delayed tooth movement period. In addition, with the extension of the application of orthodontic stress, the mRNA and protein expression levels of VEGF, PI3K, AKT and eNOS in the gingiva of the O and FO groups showed a trend of increasing at first and subsequently decreasing, which corresponds with the tooth movement cycle. In conclusion, chronic fluorosis may inhibit the angiogenesis and the expression of the VEGF/PI3K/AKT/eNOS pathway in gingival tissue of orthodontic tooth movement.

View Figures

View References

1	Srivastava S and Flora SJS: Fluoride in drinking water and skeletal fluorosis: A review of the global impact. Curr Environ Health Rep. 7:140–146. 2020.PubMed/NCBI View Article : Google Scholar
2	Meena L and Gupta R: Skeletal fluorosis. N Engl J Med. 385(1510)2021.PubMed/NCBI View Article : Google Scholar
3	Vandana KL, Srishti Raj B and Desai R: Dental fluorosis and periodontium: An original research report of in vitro and in vivo institutional studies. Biol Trace Elem Res. 199:3579–3592. 2021.PubMed/NCBI View Article : Google Scholar
4	Yue Y, Chen Z, Xie B and Yao HL: Expression of vascular endothelial growth factor in periodontal tissues during orthodontic tooth movement and its role in bone remodeling. Shanghai Kou Qiang Yi Xue. 27:18–21. 2018.PubMed/NCBI(In Chinese).
5	Narimiya T, Wada S, Kanzaki H, Ishikawa M, Tsuge A, Yamaguchi Y and Nakamura Y: Orthodontic tensile strain induces angiogenesis via type IV collagen degradation by matrix metalloproteinase-12. J Periodontal Res. 52:842–852. 2017.PubMed/NCBI View Article : Google Scholar
6	Wang XQ, Zheng LL and Ma HF: The effect of dental fluorosis on its tooth movement distance and extraction wound alveolar bone remodeling during orthodontic extraction treatment. Chin J Endemic Dis Control. 33:393–394. 2018.
7	Ding X, Jia Y, Liu C, Yang SR, Lai LY, Yang H and Ding Q: Changes in displacement and rate of orthodontic tooth movement in SD rats with chronic fluorosis. Chin J Tissue Eng Res. 26:4687–4692. 2022.
8	Lai LY, Jia Y, Ding X, Hu J and Chen B: Changes in the internal environment and shear mechanical properties of the jawbone in SD rats exposed to fluoride at different stages. Environ Occup Med. 40:95–100. 2023.
9	Yang S, Liu C, Ding Q, Yang H and Jia Y: Comparative study on fluoride accumulation in hard tissue of rats with chronic drinking-water-borne fluorosis. J Environ Occup Med. 39:174–178. 2022.
10	Liu Y, Li CX, Nie J, Mi CB and Li YM: Interactions between orthodontic treatment and gingival tissue. Chin J Dent Res. 26:11–18. 2023.PubMed/NCBI View Article : Google Scholar
11	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001.PubMed/NCBI View Article : Google Scholar
12	Dey Bhowmik A, Das T and Chattopadhyay A: Chronic exposure to environmentally relevant concentration of fluoride impairs osteoblast's collagen synthesis and matrix mineralization: Involvement of epigenetic regulation in skeletal fluorosis. Environ Res. 236(116845)2023.PubMed/NCBI View Article : Google Scholar
13	Miranda GHN, Gomes BAQ, Bittencourt LO, Aragão WAB, Nogueira LS, Dionizio AS, Buzalaf MAR, Monteiro MC and Lima RR: Chronic exposure to sodium fluoride triggers oxidative biochemistry misbalance in mice: Effects on peripheral blood circulation. Oxid Med Cell Longev. 2018(8379123)2018.PubMed/NCBI View Article : Google Scholar
14	Wu CX, Wang YH, Li Y, Guan ZZ and Qi XL: Changes of DNA repair gene methylation in blood of chronic fluorosis patients and rats. J Trace Elem Med Biol. 50:223–228. 2018.PubMed/NCBI View Article : Google Scholar
15	Huang Y, Sun M, Li F, Li H and Jiang Z: Preliminary study of mechanisms of fluoride-induced suppression of nitric oxide synthesis in human umbilical vein endothelial cells. Biol Trace Elem Res. 185:311–315. 2018.PubMed/NCBI View Article : Google Scholar
16	Noguchi T, Kitaura H, Marahleh A, Ohori F, Nara Y, Pramusita A, Kinjo R, Ma J, Kanou K and Mizoguchi I: Tumor necrosis factor-α enhances the expression of vascular endothelial growth factor in a mouse orthodontic tooth movement model. J Dent Sci. 17:415–420. 2022.PubMed/NCBI View Article : Google Scholar
17	Lu JM, Zhang ZZ, Ma X, Fang SF and Qin XH: Repression of microRNA-21 inhibits retinal vascular endothelial cell growth and angiogenesis via PTEN dependent-PI3K/Akt/VEGF signaling pathway in diabetic retinopathy. Exp Eye Res. 190(107886)2020.PubMed/NCBI View Article : Google Scholar
18	Li C, Zhou XY, Yang SR, Li ZW and Jia Y: Mechanism and cross-talk of signaling pathways associated with bone damage in fluorosis. J Environ Occup Med. 38:794–800. 2021.
19	Tao X, Liu K, Li W, Zhao S, Liu C, Dai Q, Dong T, Wei P, Duan J, Wang J and Xi M: Saponin of Aralia taibaiensis promotes angiogenesis through VEGF/VEGFR2 signaling pathway in cerebral ischemic mice. J Ethnopharmacol. 317(116771)2023.PubMed/NCBI View Article : Google Scholar
20	Chen T, Chen H, Fu Y, Liu X, Huang H, Li Z and Li S: The eNOS-induced leonurine's new role in improving the survival of random skin flap. Int Immunopharmacol. 124(111037)2023.PubMed/NCBI View Article : Google Scholar
21	Jeon HH, Teixeira H and Tsai A: Mechanistic insight into orthodontic tooth movement based on animal studies: A critical review. J Clin Med. 10(1733)2021.PubMed/NCBI View Article : Google Scholar
22	Li Y, Zhan Q, Bao M, Yi J and Li Y: Biomechanical and biological responses of periodontium in orthodontic tooth movement: Up-date in a new decade. Int J Oral Sci. 13(20)2021.PubMed/NCBI View Article : Google Scholar
23	Jiang Y, Guan Y, Lan Y, Chen S, Li T, Zou S, Hu Z and Ye Q: Mechanosensitive piezo1 in periodontal ligament cells promotes alveolar bone remodeling during orthodontic tooth movement. Front Physiol. 12(767136)2021.PubMed/NCBI View Article : Google Scholar
24	Wang Y, Lu YH, Tang C, Xue M, Li XY, Chang YP, Cheng Y, Li T, Yu XC, Sun B, et al: Calcium dobesilate restores autophagy by inhibiting the VEGF/PI3K/AKT/mTOR signaling pathway. Front Pharmacol. 10(886)2019.PubMed/NCBI View Article : Google Scholar