DOI QR코드

DOI QR Code

Influence of 10-Methacryloyloxydecyl Dihydrogen Phosphate on Cellular Senescence in Osteoblast-Like Cells

  • Ju Yeon Ban (Department of Dental Pharmacology, College of Dentistry, Dankook University) ;
  • Sang-Im Lee (Department of Dental Hygiene, College of Health Science, Dankook University)
  • 투고 : 2023.10.13
  • 심사 : 2023.11.10
  • 발행 : 2023.12.31

초록

Background: Resin-based dental materials release residual monomers or other substances from incomplete polymerization into the oral cavity, thereby causing adverse biological effects on oral tissue. 10-Methacryloyloxydecyl dihydrogen phosphate (10-MDP), an acidic monomer containing dihydrogen phosphate and methacrylate groups, is the most commonly used component of resin-based dental materials, such as restorative composite resins, dentin adhesives, and resin cements. Although previous studies have reported the cytotoxicity and biocompatibility in various cultured cells, the effects of resin monomers on cellular aging have not been reported to date. Therefore, this study aimed to investigate the effects of the resin monomer 10-MDP on cellular senescence and inflamm-aging in vitro. Methods: After stimulation with 10-MDP, MC3T3-E1 osteoblast-like cells were examined for cell viability by WST-8 assay and reactive oxygen species (ROS) production by flow cytometry. The protein and mRNA levels of molecular markers of aging were determined by western blotting and RT-PCR analysis, respectively. Results: Treatment with 0.05 to 1 mM 10-MDP for 24 hours reduced the survival of MC3T3-E1 cells in a concentration-dependent manner. The intracellular ROS levels in the 10-MDP-treated experimental group were significantly higher than those in the control group. 10-MDP at a concentration of 0.1 mM increased p53, p16, and p21 protein levels. Additionally, an aging pattern was observed with blue staining due to intracellular senescence-associated beta-galactosidase activity. Treatment with 10-MDP increased the levels of tumor necrosis factor-α, interleukin (IL)-1β, IL-6 and IL-8, however their expression was decreased by mitogen-activated-protein-kinase (MAPK) inhibitors. Conclusion: Taken together, these results suggest that the exposure of osteoblast-like cells to the dental resin monomer 10-MDP, increases the level of cellular senescence and the inflammatory response is mediated by the MAPK pathway.

키워드

과제정보

This research was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIP) (No. 2022R1F1A1076563).

참고문헌

  1. Franceschi C, Campisi J: Chronic inflammation (inflammaging) and its potential contribution to age-associated diseases. J Gerontol A Biol Sci Med Sci 69 Suppl 1: S4-S9, 2014. https://doi.org/10.1093/gerona/glu057
  2. Freund A, Orjalo AV, Desprez PY, Campisi J: Inflammatory networks during cellular senescence: causes and consequences. Trends Mol Med 16: 238-246, 2010. https://doi.org/10.1016/j.molmed.2010.03.003
  3. Hearps AC, Martin GE, Angelovich TA, et al.: Aging is associated with chronic innate immune activation and dysregulation of monocyte phenotype and function. Aging Cell 11: 867-875, 2012. https://doi.org/10.1111/j.1474-9726.2012.00851.x
  4. Ikegami K, Yamashita M, Suzuki M, et al.: Cellular senescence with SASP in periodontal ligament cells triggers inflammation in aging periodontal tissue. Aging (Albany NY) 15: 1279-1305, 2023. https://doi.org/10.18632/aging.204569
  5. Cramer NB, Stansbury JW, Bowman CN: Recent advances and developments in composite dental restorative materials. J Dent Res 90: 402-416, 2011. https://doi.org/10.1177/0022034510381263
  6. Kim EC, Park H, Lee SI, Kim SY: Effect of the acidic dental resin monomer 10-methacryloyloxydecyl dihydrogen phosphate on odontoblastic differentiation of human dental pulp cells. Basic Clin Pharmacol Toxicol 117: 340-349, 2015. https://doi.org/10.1111/bcpt.12404
  7. Kraus D, Wolfgarten M, Enkling N, et al.: In-vitro cytocompatibility of dental resin monomers on osteoblast-like cells. J Dent 65: 76-82, 2017. https://doi.org/10.1016/j.jdent.2017.07.008
  8. Ebersole JL, Graves CL, Gonzalez OA, et al.: Aging, inflammation, immunity and periodontal disease. Periodontol 2000 72: 54-75, 2016. https://doi.org/10.1111/prd.12135
  9. Watanabe S, Kawamoto S, Ohtani N, Hara E: Impact of senescence-associated secretory phenotype and its potential as a therapeutic target for senescence-associated diseases. Cancer Sci 108: 563-569, 2017. https://doi.org/10.1111/cas.13184
  10. Chang HH, Guo MK, Kasten FH, et al.: Stimulation of glutathione depletion, ROS production and cell cycle arrest of dental pulp cells and gingival epithelial cells by HEMA. Biomaterials 26: 745-753, 2005. https://doi.org/10.1016/j.biomaterials.2004.03.021
  11. Chang MC, Lin LD, Chan CP, et al.: The effect of BisGMA on cyclooxygenase-2 expression, PGE2 production and cytotoxicity via reactive oxygen species- and MEK/ERK-dependent and -independent pathways. Biomaterials 30: 4070-4077, 2009. https://doi.org/10.1016/j.biomaterials.2009.04.034
  12. Bakopoulou A, Leyhausen G, Volk J, et al.: Effects of HEMA and TEDGMA on the in vitro odontogenic differentiation potential of human pulp stem/progenitor cells derived from deciduous teeth. Dent Mater 27: 608-617, 2011. https://doi.org/10.1016/j.dental.2011.03.002
  13. Chang MC, Chen LI, Chan CP, et al.: The role of reactive oxygen species and hemeoxygenase-1 expression in the cytotoxicity, cell cycle alteration and apoptosis of dental pulp cells induced by BisGMA. Biomaterials 31: 8164-8171, 2010. https://doi.org/10.1016/j.biomaterials.2010.07.049
  14. Rea IM, Gibson DS, McGilligan V, McNerlan SE, Alexander HD, Ross OA: Age and age-related diseases: role of inflammation triggers and cytokines. Front Immunol 9: 586, 2018. https://doi.org/10.3389/fimmu.2018.00586
  15. Singh T, Newman AB: Inflammatory markers in population studies of aging. Ageing Res Rev 10: 319-329, 2011. https://doi.org/10.1016/j.arr.2010.11.002
  16. Schweikl H, Spagnuolo G, Schmalz G: Genetic and cellular toxicology of dental resin monomers. J Dent Res 85:870-877, 2006. https://doi.org/10.1177/154405910608501001
  17. Kim RH, Kang MK, Kim T, et al.: Regulation of p53 during senescence in normal human keratinocytes. Aging Cell 14:838-846, 2015. https://doi.org/10.1111/acel.12364
  18. Zhao P, Yue Z, Nie L, et al.: Hyperglycaemia-associated macrophage pyroptosis accelerates periodontal inflammaging. J Clin Periodontol 48: 1379-1392, 2021. https://doi.org/10.1111/jcpe.13517
  19. Aquino-Martinez R, Eckhardt BA, Rowsey JL, et al.: Senescent cells exacerbate chronic inflammation and contribute to periodontal disease progression in old mice. J Periodontol 92: 1483-1495, 2021. https://doi.org/10.1002/JPER.20-0529
  20. Jun NR, Jang JH, Lee JY, Lee SI: Autophagy may mediate cellular senescence by nicotine stimulation in gingival fibroblasts. J Dent Hyg Sci 22: 164-170, 2022. https://doi.org/10.17135/jdhs.2022.22.3.164
  21. Lee SI: Expression of senescence-associated secretory phenotype in senescent gingival fibroblasts. J Dent Hyg Sci 23: 169-175, 2023. https://doi.org/10.17135/jdhs.2023.23.2.169