THE PROLIFERATIVE ACTIVITY OF FIBROBLASTS OF GINGIVA IN ADULTS AT CHRONIC PERIODONTITIS

Periodontitis is a disease that progresses with age and contributes to the biological aging of the dentition. One of the reasons for this phenomenon is the aging of human gum fibroblasts. Low-intensity laser therapy stimulates the release of growth factors from fibroblasts and their division. The aim of the study was to determine the number, proliferative activity and apoptosis of gingival fibroblasts in people without signs of periodontal inflammation, with chronic periodontitis and after laser therapy. We used biopsy material obtained for periodontal, surgical, orthopedic and orthodontic indications under infiltration anesthesia in two age groups of patients aged 20–40 and 41–60 years. Cell markers Ki-67 and p53 were detected by immunohistochemical methods, the total number of gingival fibroblasts was estimated by staining with hematoxylin and eosin. The results of the conducted studies showed that the number of fibroblasts in the connective tissue lamina of the gums has age-related features. In young people from 20 to 40 years, the number of fibroblasts in gum preparations is 1,12 times higher than in people aged 41–60 years. Among the reasons for the decrease in the number of gingival fibroblasts is a decrease in their proliferative activity and activation of the proapoptotic p53 protein with age. Chronic periodontal inflammation leads to a significant increase in the number of fibroblasts, regardless of the age of the subjects. Fibroblast proliferation and p53 protein expression were more sensitive to microbial inflammation in patients aged 41 to 60 years compared to younger patients. Three-fold laser exposure had a differentiated modulating effect on the state of the gingival fibroblast population, depending on the age of the patients, the number of gingival fibroblasts was restored to the levels characteristic of healthy people, and this was observed only in the group of young patients. Thus, the number of fibroblasts in the human gingival connective tissue lamina changes with age, under conditions of inflammation and under the influence of a diode laser, which must be taken into account in dental practice.

1. Wellapuli N, Ekanayake L. Prevalence, severity and extent of chronic periodontitis among Sri Lankan adults. Community Dent Health. 2017;34(3):152-156. DOI:10.1922/CDH_4070Wellapuli05

2. Nguyen LM, Chon JJ, Kim EE et al. Biological Aging and Periodontal Disease: Analysis of NHANES (2001-2002). JDR Clin Trans Res. 2022;7(2):145-153. DOI:10.1177/2380084421995812

3. Kang Y, Yang R, Wei Z et al. Phenytoin sodium-ameliorated gingival fibroblast aging is associated with autophagy. J Periodontal Res. 2020;55(5):642-650. DOI:10.1111/jre.12750

4. Soares ASLS, Scelza MZ, Spoladore J et al. Comparison of primary human gingival fibroblasts from an older and a young donor on the evaluation of cytotoxicity of denture adhesives. J Appl Oral Sci. 2018;26:e20160594. DOI:10.1590/1678-7757-2016-0594

5. Cáceres M, Oyarzun A, Smith PC. Defective Wound-healing in Aging Gingival Tissue. J Dent Res. 2014;93(7):691-707. DOI:10.1177/0022034514533126

6. Boström EA, Kindstedt E, Sulniute R et al. Increased Eotaxin and MCP-1 Levels in Serum from Individuals with Periodontitis and in Human Gingival Fibroblasts Exposed to Pro-Inflammatory Cytokines. PLoS One. 2015;10(8):e0134608. DOI:10.1371/journal.pone.0134608

7. Bulut S, Uslu H, Ozdemir BH, Bulut OE. Expression of caspase-3, p53 and Bcl-2 in generalized aggressive periodontitis. Head Face Med. 2006;2:17. DOI:10.1186/1746-160X-2-17

8. Sharma P, Wadhwan V, Aggarwal P, Sharma A. Oral verrucous hyperplasia versus oral verrucous carcinoma: A clinicopathologic dilemma revisited using p53 as immunohistochemical marker. J Oral Maxillofac Pathol. 2016; 20(3):362-368. DOI:10.4103/0973-029X.190902

9. Shivanaikar SS, Faizuddin M, Bhat K. Effect of smoking on neutrophil apoptosis in chronic periodontitis: an immunohistochemical study. Indian J Dent Res. 2013;24(1):147. DOI:10.4103/0970-9290.114935

10. Kiyoshima T, Enoki N, Kobayashi I et al. Oxidative stress caused by a low concentration of hydrogen peroxide induces senescence-like changes in mouse gingival fibroblasts. Int J Mol Med. 2012;30(5):1007-1012. DOI:10.3892/ijmm.2012.1102

11. Ahmed AG, Raziq AH. Evaluation of Light-Emitting Diodes' Effects on the Expression Level of P53 and EGFR in the Gingival Tissues of Albino Rats. Medicina (Kaunas). 2019;55(9):605. DOI:10.3390/medicina55090605

12. Sağlam M, Köseoğlu S, Pekbağrıyanık T et al. Effects of high power-pulsed Nd:YAG laser irradiation on the release of transforming growth factor-beta (TGF-β) and vascular endothelial growth factor (VEGF) from human gingival fibroblasts. J Cosmet Laser Ther. 2017;19(8):469-474. DOI:10.1080/14764172.2017.1342042

13. Basso FG, Soares DG, Pansani TN et al. Response of a co-culture model of epithelial cells and gingival fibroblasts to zoledronic acid. Braz Oral Res. 2016;30(1):e122. DOI:10.1590/1807-3107BOR-2016.vol30.0122

14. Malgikar S, Reddy SH, Sagar SV et al. Clinical effects of photodynamic and low-level laser therapies as an adjunct to scaling and root planing of chronic periodontitis: A split-mouth randomized controlled clinical trial. Indian J Dent Res. 2016;27(2):121-126. DOI:10.4103/0970-9290.183130

15. Baima G, Romandini M, Citterio F et al. Periodontitis and Accelerated Biological Aging: A Geroscience Approach. J Dent Res. 2022;101(2):125-132. DOI:10.1177/00220345211037977

16. Golubtsova NN, Kornilova NK, Gunin AG. Vozrastnye izmeneniya soderzhaniya serin-arginin proteinkinazy 1 (SRPK1) v derme cheloveka. Uspekhi gerontologii. 2017;30(5):652-658. In Russian

17. Gunin AG, Golubtzova NN, Kornilova NK. Mekhanochuvstvitel'ny YES-assotsiirovanny protein v kozhe cheloveka v protsesse stareniya. Uspekhi Gerontologii. 2019;32(4):509-515. In Russian

18. Páez J, Hernández R, Espinoza J et al. Uncoupled inflammatory, proliferative, and cytoskeletal responses in senescent human gingival fibroblasts. J Periodontal Res. 2020;55(3):432-440. DOI:10.1111/jre.12727

19. Mijit M, Caracciolo V, Melillo A et al. Role of p53 in the Regulation of Cellular Senescence. Biomolecules. 2020;10(3):420. DOI:10.3390/biom10030420

20. Liu J, Wang X, Zheng M, Luan Q. Oxidative stress in human gingival fibroblasts from periodontitis versus healthy counterparts. Oral Dis. 2021. DOI:10.1111/odi.14103

21. Ohsugi Y, Niimi H, Shimohira T et al. In Vitro Cytological Responses against Laser Photobiomodulation for Periodontal Regeneration. Int J Mol Sci. 2020;21(23):9002. DOI:10.3390/ijms21239002