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Irradiation with a red light-emitting diode enhances the proliferation of stem cells of apical papilla via the ERK5 signalling pathway

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Abstract

This Querystudy aimed to investigate the effects of low-energy red light-emitting diode (LED) irradiation on the proliferation of stem cells from apical papilla (SCAPs) and preliminarily elucidated the underlying molecular mechanisms. SCAPs were isolated and identified in vitro. The light source was a 10 W red LED with continuous output and a wavelength of 600–700 nm. SCAPs were irradiated with 0 (control group), 0.5 J/cm2, 1 J/cm2, 3 J/cm2, or 5 J/cm2. Cell Counting Kit-8 (CCK-8) assays were used to analyze cell proliferation rates and determine the most effective concentration of extracellular signal-regulated kinase 5 (ERK5) blocker, BIX02189. A real-time polymerase chain reaction (RT-PCR) was carried out to determine the involvement of the ERK5 signalling pathway and proliferation-associated genes (C-Jun, Jun B, and Cyclin D1). 5-Ethynyl-2′-deoxyuridine (EDU) was used to analyze cell cycle kinetic parameters. CCK-8 assay results suggested that SCAPs in red LED groups exhibited a higher proliferation rate than those in the control group, and 10 μmol/L BIX02189 was the most effective blocker. The RT-PCR results demonstrate that red LEDs upregulated the expression of the ERK5, C-Jun, Jun B, and Cyclin D1 genes, and BIX02189 successfully blocked the ERK5 signalling pathway. The results of EdU staining indicated that red LED promoted DNA synthesis activity and that BIX02189 suppressed cells into S phase. Red LEDs irradiation enhances the proliferation of SCAPs via the ERK5 signalling pathway by upregulating the expression of C-Jun, Jun B, and Cyclin D1.

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All data generated or analyzed during this study are included in this published article and its supplementary information files.

References

  1. Kolios G, Moodley Y (2013) Introduction to stem cells and regenerative medicine. Respiration 85(1):3–10. https://doi.org/10.1159/000345615

    Article  PubMed  Google Scholar 

  2. Sonoyama W, Liu Y, Fang D, Yamaza T, Seo BM, Zhang C, Liu H, Gronthos S, Wang CY, Wang S, Shi S (2006) Mesenchymal stem cell-mediated functional tooth regeneration in swine. PLoS One 1(1):e79. https://doi.org/10.1371/journal.pone.0000079

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Sonoyama W, Liu Y, Yamaza T, Tuan RS, Wang S, Shi S, Huang GT (2008) Characterization of the apical papilla and its residing stem cells from human immature permanent teeth: a pilot study. J Endod 34(2):166–171. https://doi.org/10.1016/j.joen.2007.11.021

    Article  PubMed  PubMed Central  Google Scholar 

  4. Chen K, Xiong H, Huang Y, Liu C (2013) Comparative analysis of in vitro periodontal characteristics of stem cells from apical papilla (SCAP) and periodontal ligament stem cells (PDLSCs). Arch Oral Biol 58(8):997–1006. https://doi.org/10.1016/j.archoralbio.2013.02.010

    Article  CAS  PubMed  Google Scholar 

  5. Mester A, Mester A (2017) The history of photobiomodulation: Endre Mester (1903–1984). Photomed Laser Surg 35(8):393–394. https://doi.org/10.1089/pho.2017.4332

    Article  PubMed  Google Scholar 

  6. Ablon G (2018) Phototherapy with light emitting diodes: treating a broad range of medical and aesthetic conditions in dermatology. J Clin Aesthet Dermat 11(2):21–27

    Google Scholar 

  7. Barolet D (2008) Light-emitting diodes (LEDs) in dermatology. Semin Cutan Med Surg 27(4):227–238. https://doi.org/10.1016/j.sder.2008.08.003

    Article  CAS  PubMed  Google Scholar 

  8. Peng F, Wu H, Zheng Y, Xu X, Yu J (2012) The effect of noncoherent red light irradiation on proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells. Lasers Med Sci 27(3):645–653. https://doi.org/10.1007/s10103-011-1005-z

    Article  PubMed  Google Scholar 

  9. Li WT, Leu YC, Wu JL (2010) Red-light light-emitting diode irradiation increases the proliferation and osteogenic differentiation of rat bone marrow mesenchymal stem cells. Photomed Laser Surg 28(Suppl 1):S157–S165. https://doi.org/10.1089/pho.2009.2540

    Article  CAS  PubMed  Google Scholar 

  10. Chang B, Qiu H, Zhao H, Yang X, Wang Y, Ji T, Zhang Y, Quan Q, Li Y, Zeng J, Meng H, Gu Y (2019) The effects of photobiomodulation on MC3T3-E1 cells via 630 nm and 810 nm light-emitting diode. Med Sci Mon 25:8744–8752. https://doi.org/10.12659/MSM.920396

    Article  CAS  Google Scholar 

  11. Asai T, Suzuki H, Kitayama M, Matsumoto K, Kimoto A, Shigeoka M, Komori T (2014) The long-term effects of red light-emitting diode irradiation on the proliferation and differentiation of osteoblast-like MC3T3-E1 cells. Kobe J Med Sci 60(1):E12–E18

    PubMed  Google Scholar 

  12. Vale K, Maria DA, Picoli LC, Deana AM, Mascaro MB, Ferrari R, Bussadori SK, Fernandes K (2017) The effects of photobiomodulation delivered by light-emitting diode on stem cells from human exfoliated deciduous teeth: a study on the relevance to pluripotent stem cell viability and proliferation. Photomed Laser Surg 35(12):659–665. https://doi.org/10.1089/pho.2017.4279

    Article  CAS  PubMed  Google Scholar 

  13. Yamauchi N, Taguchi Y, Kato H, Umeda M (2018) High-power, red-light-emitting diode irradiation enhances proliferation, osteogenic differentiation, and mineralization of human periodontal ligament stem cells via ERK signaling pathway. J Periodontol 89(3):351–360. https://doi.org/10.1002/JPER.17-0365

    Article  CAS  PubMed  Google Scholar 

  14. Flores K, Yadav SS, Katz AA, Seger R (2019) The nuclear translocation of mitogen-activated protein kinases: molecular mechanisms and use as novel therapeutic target. Neuroendocrinology 108(2):121–131. https://doi.org/10.1159/000494085

    Article  CAS  PubMed  Google Scholar 

  15. Pan CC, Bloodworth JC, Mythreye K, Lee NY (2012) Endoglin inhibits ERK-induced c-Myc and cyclin D1 expression to impede endothelial cell proliferation. Biochem Biophys Res Commun 424(3):620–623. https://doi.org/10.1016/j.bbrc.2012.06.163

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Kato Y, Kravchenko VV, Tapping RI, Han J, Ulevitch RJ, Lee JD (1997) BMK1/ERK5 regulates serum-induced early gene expression through transcription factor MEF2C. EMBO J 16(23):7054–7066. https://doi.org/10.1093/emboj/16.23.7054

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Kato Y, Tapping RI, Huang S, Watson MH, Ulevitch RJ, Lee JD (1998) Bmk1/Erk5 is required for cell proliferation induced by epidermal growth factor. Nature 395(6703):713–716. https://doi.org/10.1038/27234

    Article  CAS  PubMed  Google Scholar 

  18. Chen C, Wu S, Lin X, Wu D, Fischbach S, Xiao X (2018) ERK5 plays an essential role in gestational beta-cell proliferation. Cell Prolif 51(3):e12410. https://doi.org/10.1111/cpr.12410

    Article  CAS  PubMed  Google Scholar 

  19. Wu Y, Zhu T, Yang Y, Gao H, Shu C, Chen Q, Yang J, Luo X, Wang Y (2021) Irradiation with red light-emitting diode enhances proliferation and osteogenic differentiation of periodontal ligament stem cells. Lasers Med Sci 36(7):1535–1543. https://doi.org/10.1007/s10103-021-03278-1

    Article  PubMed  Google Scholar 

  20. Liu C, Xiong H, Chen K, Huang Y, Huang Y, Yin X (2016) Long-term exposure to pro-inflammatory cytokines inhibits the osteogenic/dentinogenic differentiation of stem cells from the apical papilla. Int Endod J 49(10):950–959. https://doi.org/10.1111/iej.12551

    Article  CAS  PubMed  Google Scholar 

  21. Abuarqoub D, Awidi A, Abuharfeil N (2015) Comparison of osteo/odontogenic differentiation of human adult dental pulp stem cells and stem cells from apical papilla in the presence of platelet lysate. Arch Oral Biol 60(10):1545–1553. https://doi.org/10.1016/j.archoralbio.2015.07.007

    Article  CAS  PubMed  Google Scholar 

  22. Huang GT, Sonoyama W, Liu Y, Liu H, Wang S, Shi S (2008) The hidden treasure in apical papilla: the potential role in pulp/dentin regeneration and bioroot engineering. Journal of endodontics 34(6):645–651. https://doi.org/10.1016/j.joen.2008.03.001

    Article  PubMed  PubMed Central  Google Scholar 

  23. Páral P, Báječný M, Savvulidi F, Nečas E (2020) Cell cycle analysis using in vivo staining of DNA-synthesizing cells. Methods Mol Biol 2150:141–152. https://doi.org/10.1007/7651_2019_228

    Article  CAS  PubMed  Google Scholar 

  24. Nada OA, El Backly RM (2018) Stem cells from the apical papilla (SCAP) as a tool for endogenous tissue regeneration. Front Bioeng Biotechnol 6:103. https://doi.org/10.3389/fbioe.2018.00103

    Article  PubMed  PubMed Central  Google Scholar 

  25. Hadis MA, Zainal SA, Holder MJ, Carroll JD, Cooper PR, Milward MR, Palin WM (2016) The dark art of light measurement: accurate radiometry for low-level light therapy. Lasers Med Sci 31(4):789–809. https://doi.org/10.1007/s10103-016-1914-y

    Article  PubMed  PubMed Central  Google Scholar 

  26. AlGhamdi KM, Kumar A, Moussa NA (2012) Low-level laser therapy: a useful technique for enhancing the proliferation of various cultured cells. Lasers Med Sci 27(1):237–249. https://doi.org/10.1007/s10103-011-0885-2

    Article  PubMed  Google Scholar 

  27. Wu YH, Wang J, Gong DX, Gu HY, Hu SS, Zhang H (2012) Effects of low-level laser irradiation on mesenchymal stem cell proliferation: a microarray analysis. Lasers Med Sci 27(2):509–519. https://doi.org/10.1007/s10103-011-0995-x

    Article  PubMed  Google Scholar 

  28. Moore P, Ridgway TD, Higbee RG, Howard EW, Lucroy MD (2005) Effect of wavelength on low-intensity laser irradiation-stimulated cell proliferation in vitro. Lasers Surg Med 36(1):8–12. https://doi.org/10.1002/lsm.20117

    Article  PubMed  Google Scholar 

  29. Schindl A, Merwald H, Schindl L, Kaun C, Wojta J (2003) Direct stimulatory effect of low-intensity 670 nm laser irradiation on human endothelial cell proliferation. Br J Dermatol 148(2):334–336. https://doi.org/10.1046/j.1365-2133.2003.05070.x

    Article  CAS  PubMed  Google Scholar 

  30. Zhu T, Wu Y, Zhou X, Yang Y, Wang Y (2019) Irradiation by blue light-emitting diode enhances osteogenic differentiation in gingival mesenchymal stem cells in vitro. Lasers Med Sci 34(7):1473–1481. https://doi.org/10.1007/s10103-019-02750-3

    Article  PubMed  Google Scholar 

  31. Yang Y, Zhu T, Wu Y, Shu C, Chen Q, Yang J, Luo X, Wang Y (2020) Irradiation with blue light-emitting diode enhances osteogenic differentiation of stem cells from the apical papilla. Lasers Med Sci 35(9):1981–1988. https://doi.org/10.1007/s10103-020-02995-3

    Article  PubMed  Google Scholar 

  32. Tatake RJ, O’Neill MM, Kennedy CA, Wayne AL, Jakes S, Wu D, Kugler SZ Jr, Kashem MA, Kaplita P, Snow RJ (2008) Identification of pharmacological inhibitors of the MEK5/ERK5 pathway. Biochem Biophys Res Commun 377(1):120–125. https://doi.org/10.1016/j.bbrc.2008.09.087

    Article  CAS  PubMed  Google Scholar 

  33. Lee JD, Ulevitch RJ, Han J (1995) Primary structure of BMK1: a new mammalian map kinase. Biochem Biophys Res Commun 213(2):715–724. https://doi.org/10.1006/bbrc.1995.2189

    Article  CAS  PubMed  Google Scholar 

  34. Ding N, Geng B, Li Z, Yang Q, Yan L, Wan L, Zhang B, Wang C, Xia Y (2019) Fluid shear stress promotes osteoblast proliferation through the NFATc1-ERK5 pathway. Connect Tissue Res 60(2):107–116. https://doi.org/10.1080/03008207.2018.1459588

    Article  CAS  PubMed  Google Scholar 

  35. Ryan MT, Hoogenraad NJ (2007) Mitochondrial-nuclear communications. Annu Rev Biochem 76:701–722. https://doi.org/10.1146/annurev.biochem.76.052305.091720

    Article  CAS  PubMed  Google Scholar 

  36. Passarella S, Karu T (2014) Absorption of monochromatic and narrow band radiation in the visible and near IR by both mitochondrial and non-mitochondrial photoacceptors results in photobiomodulation. Journal of photochemistry and photobiology. B, Biology 140:344–358. https://doi.org/10.1016/j.jphotobiol.2014.07.021

    Article  CAS  PubMed  Google Scholar 

  37. Sommer AP (2019) Mitochondrial cytochrome c oxidase is not the primary acceptor for near infrared light-it is mitochondrial bound water: the principles of low-level light therapy. Annals Transl Med 7(Suppl 1):S13. https://doi.org/10.21037/atm.2019.01.43

    Article  CAS  Google Scholar 

  38. Karu T, Pyatibrat L (2011) Gene expression under laser and light-emitting diodes radiation for modulation of cell adhesion: possible applications for biotechnology. IUBMB Life 63(9):747–753. https://doi.org/10.1002/iub.514

    Article  CAS  PubMed  Google Scholar 

  39. Schafer KA (1998) The cell cycle: a review. Vet Pathol 35(6):461–478. https://doi.org/10.1177/030098589803500601

    Article  CAS  PubMed  Google Scholar 

  40. Yang CC, Ornatsky OI, McDermott JC, Cruz TF, Prody CA (1998) Interaction of myocyte enhancer factor 2 (MEF2) with a mitogen-activated protein kinase, ERK5/BMK1. Nucleic Acids Res 26(20):4771–4777. https://doi.org/10.1093/nar/26.20.4771

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Kato Y, Zhao M, Morikawa A, Sugiyama T, Chakravortty D, Koide N, Yoshida T, Tapping RI, Yang Y, Yokochi T, Lee JD (2000) Big mitogen-activated kinase regulates multiple members of the MEF2 protein family. J Biol Chem 275(24):18534–18540. https://doi.org/10.1074/jbc.M001573200

    Article  CAS  PubMed  Google Scholar 

  42. Jochum W, Passegué E, Wagner EF (2001) AP-1 in mouse development and tumorigenesis. Oncogene 20(19):2401–2412. https://doi.org/10.1038/sj.onc.1204389

    Article  CAS  PubMed  Google Scholar 

  43. Zhao L, Zhang T, Geng H, Liu ZQ, Liang ZF, Zhang ZQ, Min J, Yu DX, Zhong CY (2018) MAPK/AP-1 pathway regulates benzidine-induced cell proliferation through the control of cell cycle in human normal bladder epithelial cells. Oncol Lett 16(4):4628–4634. https://doi.org/10.3892/ol.2018.9155

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Barnes DM (1997) Cyclin D1 in mammary carcinoma. J Pathol 181(3):267–269. https://doi.org/10.1002/(SICI)1096-9896(199703)181:3%3c267::AID-PATH783%3e3.0.CO;2-X

    Article  CAS  PubMed  Google Scholar 

  45. Li T, Song T, Ni L, Yang G, Song X, Wu L, Liu B, Liu C (2014) The p-ERK-p-c-Jun-cyclinD1 pathway is involved in proliferation of smooth muscle cells after exposure to cigarette smoke extract. Biochem Biophys Res Commun 453(3):316–320. https://doi.org/10.1016/j.bbrc.2014.09.062

    Article  CAS  PubMed  Google Scholar 

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Funding

This work was supported by the Luzhou Municipal People’s Government-Southwest Medical University science and technology strategic cooperation projects of China (no. 2017LZXNYDT03). The reagents of this study were supported by this fund that came from Southwest Medical University.

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Authors and Affiliations

  1. School of Stomatology Southwest Medical University, Lu Zhou, 646000, China

    Chunxia Shu, Lan Hou, Juan Yang, Xiang Luo & Yutong Su

  2. Suining First People’s Hospital, Suining, 629000, China

    Chunxia Shu

  3. The TCM Hospital of Longquanyi District, Chengdu, 610100, China

    Qiang Chen

  4. School of Stomatology of Qingdao University, Qingdao, 266003, China

    Tingting Zhu

  5. The Affiliated Stomatology Hospital of Southwest Medical University, Lu Zhou, 646000, China

    Yao Wang

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  1. Chunxia Shu
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  2. Lan Hou
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  3. Qiang Chen
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  5. Juan Yang
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Contributions

All authors contributed to the study conception and design. Material preparation, data collection, and analysis were performed by Chunxia Shu and Lan Hou. The first draft of the manuscript was written by Chunxia Shu and Lan Hou, and the authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Yao Wang.

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Ethical approval

All procedures performed in the study were in accordance with the Ethics Committee of the Affiliated Hospital of Stomatology Southwest Medical University Certificate (contract grant 20180314001) and with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.

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Chunxia Shu and Lan Hou contributed to the work equally and should be regarded as co-first authors

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Shu, C., Hou, L., Chen, Q. et al. Irradiation with a red light-emitting diode enhances the proliferation of stem cells of apical papilla via the ERK5 signalling pathway. Lasers Med Sci 37, 2259–2268 (2022). https://doi.org/10.1007/s10103-021-03492-x

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