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Epigallocatechin gallate affects the proliferation of human alveolar osteoblasts and periodontal ligament cells, as well as promoting cell differentiation by regulating PI3K/Akt signaling pathway

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Abstract

Human periodontal ligament cells (hPDLCs) and human alveolar osteoblasts (hAOBs) play pivotal roles in periodontium. The regulatory effects of epigallocatechin gallate (EGCG) on hPDLCs and hAOBs remained unclear. This study probed into the functions of EGCG treating periodontal diseases. Cultured hAOBs and hPDLCs were passaged and observed by microscopic examination, and alkaline phosphatase (ALP) and immumohistochemical staining were performed for verification. hAOBs and hPDLCs were treated with EGCG and LY294002 + EGCG, then the proliferation of the two cells was assayed by MTT. Mineralization of the treated hAOBs and hPDLCs was detected by ALP activity experiment and Alizarin Red S staining kit. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting were performed for the detection of the expressions of differentiation-related mRNAs and PI3K/Akt signaling pathway-related proteins in the two cells. The third passage of hAOBs mainly showed triangle shape and were positive by ALP staining. hPDLCs in passage 3 adhered to the wall in spiral or radial pattern with positively stained vimentin and negatively stained keratin. Cell proliferation and ALP activity of the hAOBs and hPDLCs were increased by EGCG treatment. The mineralized nodules and expressions of differentiation-related mRNAs, the phosphorylation of PI3K and Akt of the hAOBs and hPDLCs were promoted by EGCG treatment, while the effects of LY294002 treatment were opposite to EGCG treatment. Epigallocatechin gallate affected the proliferation and differentiation of hAOBs and hPDLCs through regulating PI3K/Akt signaling pathway.

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References

  1. Barczyk M, Bolstad AI, Gullberg D. Role of integrins in the periodontal ligament: organizers and facilitators. Periodontol 2000. 2013;63(1):29–47. https://doi.org/10.1111/prd.12027.

    Article  PubMed  PubMed Central  Google Scholar 

  2. McCulloch CA, Lekic P, McKee MD. Role of physical forces in regulating the form and function of the periodontal ligament. Periodontology. 2000;2000(24):56–72.

    Article  Google Scholar 

  3. McCulloch CA, Melcher AH. Cell density and cell generation in the periodontal ligament of mice. Am J Anat. 1983;167(1):43–58. https://doi.org/10.1002/aja.1001670105.

    Article  PubMed  Google Scholar 

  4. Isaka J, Ohazama A, Kobayashi M, Nagashima C, Takiguchi T, Kawasaki H, et al. Participation of periodontal ligament cells with regeneration of alveolar bone. J Periodontol. 2001;72(3):314–23. https://doi.org/10.1902/jop.2001.72.3.314.

    Article  PubMed  Google Scholar 

  5. McCulloch CA. Progenitor cell populations in the periodontal ligament of mice. Anat Rec. 1985;211(3):258–62. https://doi.org/10.1002/ar.1092110305.

    Article  PubMed  Google Scholar 

  6. McCulloch CA, Nemeth E, Lowenberg B, Melcher AH. Paravascular cells in endosteal spaces of alveolar bone contribute to periodontal ligament cell populations. Anat Rec. 1987;219(3):233–42. https://doi.org/10.1002/ar.1092190304.

    Article  PubMed  Google Scholar 

  7. Seo BM, Miura M, Gronthos S, Bartold PM, Batouli S, Brahim J, et al. Investigation of multipotent postnatal stem cells from human periodontal ligament. Lancet (London, England). 2004;364(9429):149–55. https://doi.org/10.1016/s0140-6736(04)16627-0.

    Article  Google Scholar 

  8. Arceo N, Sauk JJ, Moehring J, Foster RA, Somerman MJ. Human periodontal cells initiate mineral-like nodules in vitro. J Periodontol. 1991;62(8):499–503. https://doi.org/10.1902/jop.1991.62.8.499.

    Article  PubMed  Google Scholar 

  9. Jonsson D, Nebel D, Bratthall G, Nilsson BO. The human periodontal ligament cell: a fibroblast-like cell acting as an immune cell. J Periodontal Res. 2011;46(2):153–7. https://doi.org/10.1111/j.1600-0765.2010.01331.x.

    Article  PubMed  Google Scholar 

  10. Nagata M, Iwasaki K, Akazawa K, Komaki M, Yokoyama N, Izumi Y, et al. Conditioned medium from periodontal ligament stem cells enhances periodontal regeneration. Tissue Eng Part A. 2017;23(9–10):367–77. https://doi.org/10.1089/ten.TEA.2016.0274.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Niemiec BA. Periodontal disease. Topics Companion Anim Med. 2008;23(2):72–80. https://doi.org/10.1053/j.tcam.2008.02.003.

    Article  Google Scholar 

  12. Lee JS, Lee JB, Cha JK, Choi EY, Park SY, Cho KS, et al. Chemokine in inflamed periodontal tissues activates healthy periodontal-ligament stem cell migration. J Clin Periodontol. 2017;44(5):530–9. https://doi.org/10.1111/jcpe.12710.

    Article  PubMed  Google Scholar 

  13. Wang J, Xie Y, Feng Y, Zhang L, Huang X, Shen X, et al. (-)-Epigallocatechingallate induces apoptosis in B lymphoma cells via caspase-dependent pathway and Bcl-2 family protein modulation. Int J Oncol. 2015;46(4):1507–15. https://doi.org/10.3892/ijo.2015.2869.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Yang CS, Wang H. Cancer preventive activities of tea catechins. Molecules (Basel, Switzerland). 2016;21(12):1679. https://doi.org/10.3390/molecules21121679.

    Article  Google Scholar 

  15. Jang JY, Lee JK, Jeon YK, Kim CW. Exosome derived from epigallocatechin gallate treated breast cancer cells suppresses tumor growth by inhibiting tumor-associated macrophage infiltration and M2 polarization. BMC Cancer. 2013;13:421. https://doi.org/10.1186/1471-2407-13-421.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Yun JH, Kim CS, Cho KS, Chai JK, Kim CK, Choi SH. (-)-Epigallocatechin gallate induces apoptosis, via caspase activation, in osteoclasts differentiated from RAW 264.7 cells. J Periodontal Res. 2007;42(3):212–8. https://doi.org/10.1111/j.1600-0765.2006.00935.x.

    Article  PubMed  Google Scholar 

  17. Vali B, Rao LG, El-Sohemy A. Epigallocatechin-3-gallate increases the formation of mineralized bone nodules by human osteoblast-like cells. J Nutr Biochem. 2007;18(5):341–7. https://doi.org/10.1016/j.jnutbio.2006.06.005.

    Article  PubMed  Google Scholar 

  18. Tepedelen BE, Soya E, Korkmaz M. Epigallocatechin-3-gallate reduces the proliferation of benign prostatic hyperplasia cells via regulation of focal adhesions. Life Sci. 2017;191:74–81. https://doi.org/10.1016/j.lfs.2017.10.016.

    Article  PubMed  Google Scholar 

  19. Pilloni A, Pompa G, Saccucci M, Di Carlo G, Rimondini L, Brama M, et al. Analysis of human alveolar osteoblast behavior on a nano-hydroxyapatite substrate: an in vitro study. BMC Oral Health. 2014;14:22. https://doi.org/10.1186/1472-6831-14-22.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Coates DE, Zafar S, Milne TJ. Quantitative Real-Time Gene Profiling of Human Alveolar Osteoblasts. Methods Mol Biol (Clifton, NJ). 2017;1537:447–59. https://doi.org/10.1007/978-1-4939-6685-1_27.

    Article  Google Scholar 

  21. Iacopino AM, Cutler CW. Pathophysiological relationships between periodontitis and systemic disease: recent concepts involving serum lipids. J Periodontol. 2000;71(8):1375–84. https://doi.org/10.1902/jop.2000.71.8.1375.

    Article  PubMed  Google Scholar 

  22. Polimeni G, Xiropaidis AV, Wikesjo UM. Biology and principles of periodontal wound healing/regeneration. Periodontology. 2000;2006(41):30–47. https://doi.org/10.1111/j.1600-0757.2006.00157.x.

    Article  Google Scholar 

  23. Cho MI, Garant PR. Development and general structure of the periodontium. Periodontology. 2000;2000(24):9–27.

    Article  Google Scholar 

  24. Gronthos S, Mankani M, Brahim J, Robey PG, Shi S. Postnatal human dental pulp stem cells (DPSCs) in vitro and in vivo. Proc Natl Acad Sci USA. 2000;97(25):13625–30. https://doi.org/10.1073/pnas.240309797.

    Article  PubMed  Google Scholar 

  25. Nagatomo K, Komaki M, Sekiya I, Sakaguchi Y, Noguchi K, Oda S, et al. Stem cell properties of human periodontal ligament cells. J Periodontal Res. 2006;41(4):303–10. https://doi.org/10.1111/j.1600-0765.2006.00870.x.

    Article  PubMed  Google Scholar 

  26. Monje A, Chan HL, Galindo-Moreno P, Elnayef B, Suarez-Lopez del Amo F, Wang F, et al. Alveolar bone architecture a systematic review and meta-analysis. J Periodontol. 2015;86(11):1231–48. https://doi.org/10.1902/jop.2015.150263.

    Article  PubMed  Google Scholar 

  27. Jung IH, Lee DE, Yun JH, Cho AR, Kim CS, You YJ, et al. Anti-inflammatory effect of (-)-epigallocatechin-3-gallate on Porphyromonas gingivalis lipopolysaccharide-stimulated fibroblasts and stem cells derived from human periodontal ligament. J Periodontal implant Sci. 2012;42(6):185–95. https://doi.org/10.5051/jpis.2012.42.6.185.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Tian B, Sun Z, Xu Z, Hua Y. Chemiluminescence analysis of the prooxidant and antioxidant effects of epigallocatechin-3-gallate. Asia Pac J Clin Nutr. 2007;16(Suppl 1):153–7.

    PubMed  Google Scholar 

  29. van Straalen JP, Sanders E, Prummel MF, Sanders GT. Bone-alkaline phosphatase as indicator of bone formation. Clin Chim Acta Int J Clin Chem. 1991;201(1–2):27–33. https://doi.org/10.1016/0009-8981(91)90021-4.

    Article  Google Scholar 

  30. Sartori EM, Magro-Filho O, Silveira Mendonca DB, Li X, Fu J, Mendonca G. Modulation of micro RNA expression and osteoblast differentiation by nanotopography. Int J Oral Maxillofac Implant. 2018;33(2):269–80. https://doi.org/10.11607/jomi.5372.

    Article  Google Scholar 

  31. Yu JS, Cui W. Proliferation, survival and metabolism: the role of PI3K/AKT/mTOR signalling in pluripotency and cell fate determination. Development (Cambridge, England). 2016;143(17):3050–60. https://doi.org/10.1242/dev.137075.

    Article  Google Scholar 

  32. Yi T, Lee HL, Cha JH, Ko SI, Kim HJ, Shin HI, et al. Epidermal growth factor receptor regulates osteoclast differentiation and survival through cross-talking with RANK signaling. J Cell Physiol. 2008;217(2):409–22. https://doi.org/10.1002/jcp.21511.

    Article  PubMed  Google Scholar 

  33. Luo KW, Lung WY, Chun X, Luo XL, Huang WR. EGCG inhibited bladder cancer T24 and 5637 cell proliferation and migration via PI3K/AKT pathway. Oncotarget. 2018;9(15):12261–72. https://doi.org/10.18632/oncotarget.24301.

    Article  PubMed  PubMed Central  Google Scholar 

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Funding

This study was supported by grants from Project of Health and Science in Zhejiang (Grant No. 2016KYB233 & 2019KY497).

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Authors and Affiliations

  1. The Affiliated Stomatologic Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China

    Cheng Ding & Huiming Wang

  2. Department of Stomatology, The Affiliated Hospital of Hangzhou Normal University, Hangzhou, Zhejiang, China

    Cheng Ding, Xing Chen & Liangjun Zhong

  3. School of Medicine, Hangzhou Normal University, Hangzhou, Zhejiang, China

    Shulei Fu, Chongchong Chen & Liangjun Zhong

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  1. Cheng Ding
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Contributions

Substantial contributions to conception and design: CD, SF. Data acquisition, data analysis and interpretation: XC, CC, HW, LZ. Drafting the article or critically revising it for important intellectual content: CD, SF. Final approval of the version to be published: all authors. Agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of the work are appropriately investigated and resolved: all authors.

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Correspondence to Huiming Wang or Liangjun Zhong.

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Research involving human participants and/or animals

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The clinical trial program had been reviewed and approved by the Ethics Committee of the Affiliated Hospital of Hangzhou Normal University (AH2017030821).

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Ding, C., Fu, S., Chen, X. et al. Epigallocatechin gallate affects the proliferation of human alveolar osteoblasts and periodontal ligament cells, as well as promoting cell differentiation by regulating PI3K/Akt signaling pathway. Odontology 109, 729–740 (2021). https://doi.org/10.1007/s10266-021-00597-1

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