Excessıve Fluorıde ıntake Alters the MMP-2, TIMP-1 and TGF-β Levels of Perıodontal Soft Tıssues: an Experımental Study ın Rabbıts

Overview

Journal Clin Oral Investig

Specialty Dentistry

Date 2011 Dec 7

PMID 22143481

Citations 3

Authors

Muge Lutfioglu

Elif Eser Sakallioglu

Umur Sakallioglu

M Yavuz Gulbahar

Mehtap Muglali

Burcu Bas

Abdurrahman Aksoy

Affiliations

Soon will be listed here.

Abstract

Objectives: This study evaluated the influence of fluoride on periodontal soft tissues by investigating any alterations in their MMP-2, TIMP-1 and TGF-β profiles secondary to excessive fluoride intake.

Material And Methods: Fluorosis was induced in 18 rabbits (test group) through consumption of fluoride added to drinking water, whereas 10 rabbits consumed regular tap water as daily supply (control group). Following fluorosis verification, animals were sacrificed and their 1st mandibular molar teeth were utilized in the assessments. MMP-2, TIMP-1 and TGF-β were separately investigated for gingival epithelium (GE), gingival connective tissue (GC) and periodontal ligament (PL) to evaluate periodontal soft tissues. Histological sections were prepared from the groups, the parameters were determined by immunohistochemistry, and their levels were calculated by quantification of the immunostainings.

Results: Staining intensity of MMP-2 in GC and PL (p < 0.01); TIMP-1 and TGF-β of GE, GC and PL (p < 0.01) were higher in the test group compared to those of the control group. Intra-group staining of TIMP-1 was higher than MMP-2 in all test group compartments (p < 0.01) and in the control group GE (p < 0.01). TIMP-1 was also higher than TGF-β in the GE and PL of the test group (p < 0.05) and in the GE of the control group (p < 0.01).

Conclusion: These results suggest that excessive fluoride intake may affect periodontal soft tissues by increasing MMP-2, TIMP-1 and TGF-β, and thereby altering the MMP-2/TIMP-1 and TIMP-1/TGF-β ratios.

Clinical Relevance: Excessive fluoride consumption may alter the periodontal tissue homeostasis which may be detrimental in the maintenance of periodontal health.

Citing Articles

Matrix Metalloproteinases in Dental and Periodontal Tissues and Their Current Inhibitors: Developmental, Degradational and Pathological Aspects.

Elgezawi M, Haridy R, Almas K, Abdalla M, Omar O, Abuohashish H Int J Mol Sci. 2022; 23(16).

PMID: 36012195 PMC: 9409155. DOI: 10.3390/ijms23168929.

Maxillary incisor enamel defects in individuals born with cleft lip/palate.

Lavor J, Lacerda R, Modesto A, Vieira A PLoS One. 2020; 15(12):e0244506.

PMID: 33370403 PMC: 7769421. DOI: 10.1371/journal.pone.0244506.

Matrix Metallopeptidase-2 Gene rs2287074 Polymorphism is Associated with Brick Tea Skeletal Fluorosis in Tibetans and Kazaks, China.

Pei J, Li B, Liu Y, Liu X, Li M, Chu Y Sci Rep. 2017; 7:40086.

PMID: 28079131 PMC: 5227713. DOI: 10.1038/srep40086.

References

Martel-Pelletier J, McCollum R, Fujimoto N, Obata K, Cloutier J, Pelletier J . Excess of metalloproteases over tissue inhibitor of metalloprotease may contribute to cartilage degradation in osteoarthritis and rheumatoid arthritis. Lab Invest. 1994; 70(6):807-15. View

Reynolds J, Hembry R, Meikle M . Connective tissue degradation in health and periodontal disease and the roles of matrix metalloproteinases and their natural inhibitors. Adv Dent Res. 1994; 8(2):312-9. DOI: 10.1177/08959374940080022701. View

Bartold P, Walsh L, Narayanan A . Molecular and cell biology of the gingiva. Periodontol 2000. 2001; 24:28-55. DOI: 10.1034/j.1600-0757.2000.2240103.x. View

Ermis R, Koray F, Akdeniz B . Dental caries and fluorosis in low- and high-fluoride areas in Turkey. Quintessence Int. 2003; 34(5):354-60. View

Ghosh D, Sarkar S, Maiti R, Jana D, Das U . Testicular toxicity in sodium fluoride treated rats: association with oxidative stress. Reprod Toxicol. 2002; 16(4):385-90. DOI: 10.1016/s0890-6238(02)00038-2. View

Waddington R, Langley M . Altered expression of matrix metalloproteinases within mineralizing bone cells in vitro in the presence of fluoride. Connect Tissue Res. 2003; 44(2):88-95. View

Kubota T, Itagaki M, Hoshino C, Nagata M, Morozumi T, Kobayashi T . Altered gene expression levels of matrix metalloproteinases and their inhibitors in periodontitis-affected gingival tissue. J Periodontol. 2008; 79(1):166-73. DOI: 10.1902/jop.2008.070159. View

Robinson C, Connell S, Kirkham J, Brookes S, Shore R, Smith A . The effect of fluoride on the developing tooth. Caries Res. 2004; 38(3):268-76. DOI: 10.1159/000077766. View

Manna P, Sinha M, Sil P . A 43 kD protein isolated from the herb Cajanus indicus L attenuates sodium fluoride-induced hepatic and renal disorders in vivo. J Biochem Mol Biol. 2007; 40(3):382-95. DOI: 10.5483/bmbrep.2007.40.3.382. View

10.

Maeso G, Bravo M, Bascones A . Levels of metalloproteinase-2 and -9 and tissue inhibitor of matrix metalloproteinase-1 in gingival crevicular fluid of patients with periodontitis, gingivitis, and healthy gingiva. Quintessence Int. 2007; 38(3):247-52. View

11.

Haikel Y, Turlot J, Cahen P, Frank R . Periodontal treatment needs in populations of high- and low-fluoride areas of Morocco. J Clin Periodontol. 1989; 16(9):596-600. DOI: 10.1111/j.1600-051x.1989.tb02144.x. View

12.

Rai B, Kharb S, Jain R, Anand S . Biomarkers of periodontitis in oral fluids. J Oral Sci. 2008; 50(1):53-6. DOI: 10.2334/josnusd.50.53. View

13.

Susheela A, Sharma K . Fluoride-induced changes in the tooth glycosaminoglycans: an in vivo study in the rabbit. Arch Toxicol. 1988; 62(4):328-30. DOI: 10.1007/BF00332496. View

14.

Hannas A, Pereira J, Granjeiro J, Tjaderhane L . The role of matrix metalloproteinases in the oral environment. Acta Odontol Scand. 2007; 65(1):1-13. DOI: 10.1080/00016350600963640. View

15.

Guan Z, Wang Y, Xiao K, Dai D, Chen Y, Liu J . Influence of chronic fluorosis on membrane lipids in rat brain. Neurotoxicol Teratol. 1998; 20(5):537-42. DOI: 10.1016/s0892-0362(97)00136-0. View

16.

Anuradha K, Chadrashekar J, Ramesh N . Prevalence of periodontal disease in endemically flourosed areas of Davangere Taluk, India. Indian J Dent Res. 2002; 13(1):15-9. View

17.

Meikle M, Hembry R, Holley J, Horton C, McFarlane C, Reynolds J . Immunolocalization of matrix metalloproteinases and TIMP-1 (tissue inhibitor of metalloproteinases) in human gingival tissues from periodontitis patients. J Periodontal Res. 1994; 29(2):118-26. DOI: 10.1111/j.1600-0765.1994.tb01100.x. View

18.

Gerlach R, de Souza A, Cury J, Line S . Fluoride effect on the activity of enamel matrix proteinases in vitro. Eur J Oral Sci. 2000; 108(1):48-53. DOI: 10.1034/j.1600-0722.2000.00735.x. View

19.

Cochran D, Wozney J . Biological mediators for periodontal regeneration. Periodontol 2000. 1999; 19:40-58. DOI: 10.1111/j.1600-0757.1999.tb00146.x. View

20.

Ravanti L, Hakkinen L, Larjava H, Saarialho-Kere U, Foschi M, Han J . Transforming growth factor-beta induces collagenase-3 expression by human gingival fibroblasts via p38 mitogen-activated protein kinase. J Biol Chem. 1999; 274(52):37292-300. DOI: 10.1074/jbc.274.52.37292. View