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Effects of histone acetyltransferase (HAT) and histone deacetylase (HDAC) inhibitors on proliferative, differentiative, and regenerative functions of Toll-like receptor 2 (TLR-2)-stimulated human dental pulp cells (hDPCs)

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Abstract

Objectives

This in vitro study aimed to modify TLR-2-mediated effects on the paracrine, proliferative, and differentiation potentials of human dental pulp–derived cells using histone acetyltransferase (HAT) and histone deacetylase (HDAC) inhibitors.

Materials and methods

Cell viability was assessed using the XTT assay. Cells were either treated with 10 μg/ml Pam3CSK4 only, or pre-treated with valproic acid (VPA) (3 mM), trichostatin A (TSA) (3 μM), and MG-149 (3 μM) for a total of 4 h and 24 h. Control groups included unstimulated cells and cells incubated with inhibitors solvents only. Transcript levels for NANOG, OCT3-4, FGF-1 and 2, NGF, VEGF, COL-1A1, TLR-2, hβD-2 and 3, BMP-2, DSPP, and ALP were assessed through qPCR.

Results

After 24 h, TSA pre-treatment significantly upregulated the defensins and maintained the elevated pro-inflammatory cytokines, but significantly reduced healing and differentiation genes. VPA significantly upregulated the pro-inflammatory cytokine levels, while MG-149 significantly downregulated them. Pluripotency genes were not significantly affected by any regimen.

Conclusions

At the attempted concentrations, TSA upregulated the defensins gene expression levels, and MG-149 exerted a remarkable anti-inflammatory effect; therefore, they could favorably impact the immunological profile of hDPCs.

Clinical relevance

Targeting hDPC nuclear function could be a promising option in the scope of the biological management of inflammatory pulp diseases.

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References

  1. Schmalz G, Smith AJ (2014) Pulp development, repair, and regeneration: challenges of the transition from traditional dentistry to biologically based therapies. J Endod 40:S2-5. https://doi.org/10.1016/j.joen.2014.01.018

    Article  PubMed  Google Scholar 

  2. Duncan HF, Smith AJ, Fleming GJP, Cooper PR (2012) Histone deacetylase inhibitors induced differentiation and accelerated mineralization of pulp-derived cells. J Endod 38(3):339–345. https://doi.org/10.1016/j.joen.2011.12.014

    Article  PubMed  Google Scholar 

  3. Kearney M, Cooper PR, Smith AJ, Duncan HF (2018) Epigenetic approaches to the treatment of dental pulp inflammation and repair: opportunities and obstacles. Front Genet 9:1–18. https://doi.org/10.3389/fgene.2018.00311

    Article  CAS  Google Scholar 

  4. Paino F, La Noce A, Tirino V, Naddeo A, Desiderio V, Pirozzi U et al (2014) Histone deacetylase inhibition with valproic acid downregulates osteocalcin gene expression in human dental pulp stem cells and osteoblasts: Evidence for HDAC2 involvement. Stem Cells 32(1):279–289. https://doi.org/10.1002/stem.1544

    Article  PubMed  CAS  Google Scholar 

  5. Jin H, Park JY, Choi H, Choung PH (2013) HDAC inhibitor trichostatin a promotes proliferation and odontoblast differentiation of human dental pulp stem cells. Tissue Eng - Part A 19(5–6):613–624. https://doi.org/10.1089/ten.TEA.2012.0163

    Article  PubMed  CAS  Google Scholar 

  6. Yang XJ, Seto E (2007) HATs and HDACs: from structure, function and regulation to novel strategies for therapy and prevention. Oncogene 26(37):5310–5318. https://doi.org/10.1038/sj.onc.1210599

    Article  PubMed  CAS  Google Scholar 

  7. Marumo T, Hishikawa K, Yoshikawa M, Hirahashi J, Kawachi S, Fujita T (2010) Histone deacetylase modulates the proinflammatory and -fibrotic changes in tubulointerstitial injury. Am J Physiol - Ren Physiol 298(1):133–141

    Article  Google Scholar 

  8. Dekker FJ, Van Den Bosch T, Martin NI (2014) Small molecule inhibitors of histone acetyltransferases and deacetylases are potential drugs for inflammatory diseases. Drug Discov Today 19(5):654–660. https://doi.org/10.1016/j.drudis.2013.11.012

    Article  PubMed  CAS  Google Scholar 

  9. Duncan HF, Smith AJ, Fleming GJP, Cooper PR (2013) Histone deacetylase inhibitors epigenetically promote reparative events in primary dental pulp cells. Exp Cell Res 319(10):1534–1543. https://doi.org/10.1016/j.yexcr.2013.02.022

    Article  PubMed  CAS  Google Scholar 

  10. Manzo F, Tambaro FP, Mai A, Altucci L (2009) Histone acetyltransferase inhibitors and preclinical studies. Expert Opin Ther Pat 19(6):761–774. https://doi.org/10.1517/13543770902895727

    Article  PubMed  CAS  Google Scholar 

  11. Ghizzoni M, Haisma HJ, Maarsingh H, Dekker FJ (2011) Histone acetyltransferases are crucial regulators in NF-κB mediated inflammation. Drug Discov Today 16(11–12):504–511. https://doi.org/10.1016/j.drudis.2011.03.009

    Article  PubMed  CAS  Google Scholar 

  12. van den Bosch T, Leus NGJ, Wapenaar H, Boichenko A, Hermans J, Bischoff R et al (2017) A 6-alkylsalicylate histone acetyltransferase inhibitor inhibits histone acetylation and pro-inflammatory gene expression in murine precision-cut lung slices. Pulm Pharmacol Ther 44:88–95. https://doi.org/10.1016/j.pupt.2017.03.006

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  13. Liu Y, Du J, Liu X, Wang L, Han Y, Huang C et al (2021) MG149 inhibits histone acetyltransferase KAT8-mediated IL-33 acetylation to alleviate allergic airway inflammation and airway hyperresponsiveness. Signal Transduct Target Ther 6(1):31–34. https://doi.org/10.1038/s41392-021-00667-4

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  14. Balasubramanyam K, Swaminathan V, Ranganathan A, Kundu TK (2003) Small molecule modulators of histone acetyltransferase p300. J Biol Chem 278(21):19134–19140. https://doi.org/10.1074/jbc.M301580200

    Article  PubMed  CAS  Google Scholar 

  15. Shayegan A, Zucchi A, De Swert K, Balau B, Truyens C, Nicaise C (2021) Lipoteichoic acid stimulates the proliferation, migration and cytokine production of adult dental pulp stem cells without affecting osteogenic differentiation. Int Endod J 54(4):585–600. https://doi.org/10.1111/iej.13448

    Article  PubMed  CAS  Google Scholar 

  16. Carrouel F, Staquet MJ, Keller JF, Baudouin C, Msika P, Bleicher F, Alliot-Licht B, Farges JC (2013) Lipopolysaccharide-binding protein inhibits toll-like receptor 2 activation by lipoteichoic acid in human odontoblast-like cells. J Endod 39(8):1008–1014. https://doi.org/10.1016/j.joen.2013.04.020

    Article  PubMed  Google Scholar 

  17. He W, Wang Z, Zhou Z, Zhang Y, Zhu Q, Wei K, Lin Y, Cooper PR, Smith AJ, Yu Q (2014) Lipopolysaccharide enhances Wnt5a expression through toll-like receptor 4, myeloid differentiating factor 88, phosphatidylinositol 3-OH kinase/AKT and nuclear factor kappa B pathways in human dental pulp stem cells. J Endod 40(1):69–75. https://doi.org/10.1016/j.joen.2013.09.011

    Article  PubMed  Google Scholar 

  18. Kraus D, Glassmann A, Golletz C, Kristiansen G, Winter J, Probstmeier R (2021) Zona pellucida protein 2 (ZP2) is expressed in colon cancer and promotes cell proliferation. Cancers 13(8):1759. https://doi.org/10.3390/cancers13081759

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  19. Najar M, Krayem M, Meuleman N, Bron D, Lagneaux L (2017) Mesenchymal stromal cells and toll-like receptor priming: a critical review. Immune Netw 17(2):89–102. https://doi.org/10.4110/in.2017.17.2.89

    Article  PubMed  PubMed Central  Google Scholar 

  20. Andrukhov O (2021) Toll-Like Receptors and Dental Mesenchymal Stromal Cells. Front Oral Health 16(2):648901. https://doi.org/10.3389/froh.2021.648901

  21. Bode KA, Schroder K, Hume DA, Ravasi T, Heeg K, Sweet MJ et al (2007) Histone deacetylase inhibitors decrease Toll-like receptor-mediated activation of proinflammatory gene expression by impairing transcription factor recruitment. Immunology 122(4):596–606. https://doi.org/10.1111/j.1365-2567.2007.02678

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  22. Keller JF, Carrouel F, Colomb E, Durand SH, Baudouin C, Msika P, Bleicher F, Vincent C, Staquet MJ, Farges JC (2010) Toll-like receptor 2 activation by lipoteichoic acid induces differential production of pro-inflammatory cytokines in human odontoblasts, dental pulp fibroblasts and immature dendritic cells. Immunobiology 215(1):53–59. https://doi.org/10.1016/j.imbio.2009.01.009

    Article  PubMed  CAS  Google Scholar 

  23. Tsolmongyn B, Koide N, Jambalganiin U, Odkhuu E, Naiki Y, Komatsu T, Yoshida T, Yokochi T (2013) A Toll-like receptor 2 ligand, Pam3CSK4, augments interferon-γ-induced nitric oxide production via a physical association between MyD88 and interferon-γ receptor in vascular endothelial cells. Immunology 140(3):352–61

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  24. Natoli G (2009) Control of NF-kappaB-dependent transcriptional responses by chromatin organization. Cold Spring Harb Perspect Biol 1(4):1–10. https://doi.org/10.1101/cshperspect.a000224

    Article  MathSciNet  CAS  Google Scholar 

  25. Zhao JL, Ma C, O’Connell RM, Mehta A, Diloreto R, Heath JR et al (2014) Conversion of danger signals into cytokine signals by hematopoietic stem and progenitor cells for regulation of stress-induced hematopoiesis. Cell Stem Cell 14(4):445–459. https://doi.org/10.1016/j.stem.2014.01.007

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  26. Zampetaki A, Xiao Q, Zeng L, Hu Y, Xu Q (2006) TLR4 expression in mouse embryonic stem cells and in stem cell-derived vascular cells is regulated by epigenetic modifications. Biochem Biophys Res Commun 347(1):89–99. https://doi.org/10.1016/j.bbrc.2006.06.055

    Article  PubMed  CAS  Google Scholar 

  27. Veerayutthwilai O, Byers MR, Pham TTT, Darveau RP, Dale BA (2007) Differential regulation of immune responses by odontoblasts. Oral Microbiol Immunol 22(1):5–13. https://doi.org/10.1111/j.1399-302X.2007.00310.x

    Article  PubMed  CAS  Google Scholar 

  28. Andrukhov O, Hong JSA, Andrukhova O, Blufstein A, Moritz A, Rausch-Fan X (2017) Response of human periodontal ligament stem cells to IFN-γ and TLR-agonists. Sci Rep 7(1):1–9. https://doi.org/10.1038/s41598-017-12480-7

    Article  Google Scholar 

  29. Blufstein A, Behm C, Gahn J, Uitz O, Naumovska I, Moritz A et al (2019) Synergistic effects triggered by simultaneous Toll-like receptor-2 and -3 activation in human periodontal ligament stem cells. J Periodontol 90(10):1190–201. https://doi.org/10.1002/JPER.19-0005

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  30. Zhu Y, Li Q, Zhou Y, Li W (2019) TLR activation inhibits the osteogenic potential of human periodontal ligament stem cells through Akt signaling in a Myd88- or TRIF-dependent manner. J Periodontol 90(4):400–415. https://doi.org/10.1002/JPER.18-0251

    Article  PubMed  CAS  Google Scholar 

  31. Go HS, Seo JE, Kim KC, Han SM, Kim PK, Kang YS et al (2011) Valproic acid inhibits neural progenitor cell death by activation of NF-B signaling pathway and up-regulation of Bcl-XL. J Biomed Sci 18(1):48. https://doi.org/10.1186/1423-0127-18-48

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  32. Li Y, Yuan Z, Liu B, Sailhamer EA, Shults C, Velmahos GC et al (2008) Prevention of hypoxia-induced neuronal apoptosis through histone deacetylase inhibition. J Trauma - Inj Infect Crit Care 64(4):863–870. https://doi.org/10.1097/TA.0b013e318166b822

    Article  CAS  Google Scholar 

  33. Roger T, Lugrin J, Le Roy D, Goy G, Mombelli M, Koessler T et al (2011) Histone deacetylase inhibitors impair innate immune responses to Toll-like receptor agonists and to infection. Blood 117(4):1205–1217. https://doi.org/10.1182/blood-2010-05-284711

    Article  PubMed  CAS  Google Scholar 

  34. Seet LF, Toh LZ, Finger SN, Chu SWL, Wong TT (2019) Valproic acid exerts specific cellular and molecular anti-inflammatory effects in post-operative conjunctiva. J Mol Med 97(1):63–75. https://doi.org/10.1007/s00109-018-1722-x

    Article  PubMed  CAS  Google Scholar 

  35. Ye J, Li J, Zhou M, Xia R, Liu R, Yu L (2016) Modulation of donor-specific antibody production after organ transplantation by valproic acid: a histone deacetylase inhibitor. Transplantation 100(11):2342–2351. https://doi.org/10.1097/TP.0000000000001197

    Article  PubMed  CAS  Google Scholar 

  36. Han SB, Lee JK (2009) Anti-inflammatory effect of trichostatin-A on murine bone marrow-derived macrophages. Arch Pharm Res 32(4):613–624. https://doi.org/10.1007/s12272-009-1418-4

    Article  PubMed  CAS  Google Scholar 

  37. Shukla S, Tekwani BL (2020) Histone deacetylases inhibitors in neurodegenerative diseases, neuroprotection and neuronal differentiation. Front Pharmacol 24(11):537. https://doi.org/10.3389/fphar.2020.00537

    Article  CAS  Google Scholar 

  38. Hancock WW, Akimova T, Beier UH, Liu Y, Wang L (2012) HDAC inhibitor therapy in autoimmunity and transplantation. Ann Rheum Dis 71(Suppl 2):i46–54. https://doi.org/10.1136/annrheumdis-2011-200593

  39. Göttlicher M, Minucci S, Zhu P, Krämer OH, Schimpf A, Giavara S, Sleeman JP, Lo Coco F, Nervi C, Pelicci PG, Heinzel T (2001) Valproic acid defines a novel class of HDAC inhibitors inducing differentiation of transformed cells. EMBO J 20(24):6969–78. https://doi.org/10.1093/emboj/20.24.6969

    Article  PubMed  PubMed Central  Google Scholar 

  40. Colamatteo A, Carbone F, Bruzzaniti S, Galgani M, Fusco C, Maniscalco GT et al (2020) Molecular mechanisms controlling Foxp3 expression in health and autoimmunity: from epigenetic to post-translational regulation. Front Immunol 10:1–20. https://doi.org/10.3389/fimmu.2019.03136

    Article  CAS  Google Scholar 

  41. Han SB, Lee JK (2009) Anti-inflammatory effect of trichostatin-A on murine bone marrow-derived macrophages. Arch Pharm Res 32(4):613–624. https://doi.org/10.1007/s12272-009-1418-4

    Article  PubMed  CAS  Google Scholar 

  42. Sato T, Kotake D, Hiratsuka M, Hirasawa N (2013) Enhancement of inflammatory protein expression and nuclear factor Κb (NF-Κb) activity by trichostatin A (TSA) in OP9 preadipocytes. PLoS One 8(3):e59702. https://doi.org/10.1371/journal.pone.0059702

  43. Kaminska B, Mota M, Pizzi M (2016) Signal transduction and epigenetic mechanisms in the control of microglia activation during neuroinflammation. Biochim Biophys Acta 1862(3):339–351. https://doi.org/10.1016/j.bbadis.2015.10.026

    Article  PubMed  CAS  Google Scholar 

  44. Dekker FJ, Haisma HJ (2009) Histone acetyl transferases as emerging drug targets. Drug Discov Today 14(19–20):942–948. https://doi.org/10.1016/j.drudis.2009.06.008

    Article  PubMed  CAS  Google Scholar 

  45. Chung WO, Dommisch H, Yin L, Dale BA (2007) Expression of defensins in gingiva and their role in periodontal health and disease. Curr Pharm Des 13(30):3073–3083. https://doi.org/10.2174/138161207782110435

    Article  PubMed  CAS  Google Scholar 

  46. Munz M, Willenborg C, Richter GM, Jockel-Schneider Y, Graetz C, Staufenbiel I, Wellmann J, Berger K, Krone B, Hoffmann P, van der Velde N, Uitterlinden AG, de Groot LCPGM, Sawalha AH, Direskeneli H, Saruhan-Direskeneli G, Guzeldemir-Akcakanat E, Keceli HG, Laudes M, Noack B, Teumer A, Holtfreter B, Kocher T, Eickholz P, Meyle J, Doerfer C, Bruckmann C, Lieb W, Franke A, Schreiber S, Nohutcu RM, Erdmann J, Loos BG, Jepsen S, Dommisch H, Schaefer AS (2017) A genome-wide association study identifies nucleotide variants at SIGLEC5 and DEFA1A3 as risk loci for periodontitis. Hum Mol Genet 26(13):2577–2588. https://doi.org/10.1093/hmg/ddx151

    Article  PubMed  CAS  Google Scholar 

  47. Fischer N, Sechet E, Friedman R, Amiot A, Sobhani I, Nigro G et al (2016) Histone deacetylase inhibition enhances antimicrobial peptide but not inflammatory cytokine expression upon bacterial challenge. Proc Natl Acad Sci U S A 113(21):E2993-3001. https://doi.org/10.1073/pnas.1605997113

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  48. Yin L, Chung WO (2011) Epigenetic regulation of human Β-defensin 2 and CC chemokine ligand 20 expression in gingival epithelial cells in response to oral bacteria. Mucosal Immunol 4(4):409–419. https://doi.org/10.1038/mi.2010.83

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  49. Stebe-Frick S, Ostaff MJ, Stange EF, Malek NP, Wehkamp J (2018) Histone deacetylase-mediated regulation of the antimicrobial peptide hBD2 differs in intestinal cell lines and cultured tissue. Sci Rep 8(1):1–11. https://doi.org/10.1038/s41598-018-31125-x

    Article  CAS  Google Scholar 

  50. Zhang J, Liu X, Yu W, Zhang Y, Shi C, Ni S, Liu Q, Li X, Sun Y, Zheng C, Sun H (2016) Effects of human vascular endothelial growth factor on reparative dentin formation. Mol Med Rep 13(1):705–712. https://doi.org/10.3892/mmr.2015.4608

    Article  PubMed  CAS  Google Scholar 

  51. Saraswati S, Marrow SMW, Watch LA, Young PP (2019) Identification of a pro-angiogenic functional role for FSP1-positive fibroblast subtype in wound healing. Nat Commun (10):p 3027. https://doi.org/10.1038/s41467-019-10965-9

  52. Lee J, Il Im G (2017) Effects of trichostatin A on the chondrogenesis from human mesenchymal stem cells. Tissue Eng Regen Med 14(4):403–10. https://doi.org/10.1007/s13770-017-0041-6

    Article  MathSciNet  PubMed  PubMed Central  CAS  Google Scholar 

  53. Huang CE, Hu FW, Yu CH, Tsai LL, Lee TH, Chou MY et al (2017) Concurrent expression of Oct4 and Nanog maintains mesenchymal stem-like property of human dental pulp cells. Int J Mol Sci 15(10):18623–18639. https://doi.org/10.3390/ijms151018623

    Article  CAS  Google Scholar 

  54. Keong JY, Low LW, Chong JM, Ong YY, Pulikkotil SJ, Singh G et al (2020) Effect of lipopolysaccharide on cell proliferation and vascular endothelial growth factor secretion of periodontal ligament stem cells. Saudi Dent J 32(3):148–154. https://doi.org/10.1016/j.sdentj.2019.08.001

    Article  PubMed  Google Scholar 

  55. Liu Y, Gao Y, Zhan X, Cui L, Xu S, Ma D et al (2014) TLR4 activation by lipopolysaccharide and Streptococcus mutans induces differential regulation of proliferation and migration in human dental pulp stem cells. J Endod 40(9):1375–1381. https://doi.org/10.1016/j.joen.2014.03.015

    Article  PubMed  Google Scholar 

  56. Sharma A, Mir R, Galande S (2021) Epigenetic regulation of the Wnt/β-Catenin signaling pathway in cancer. Front Genet 12:681053. https://doi.org/10.3389/fgene.2021.681053

  57. Lee HW, Suh JH, Kim AY, Lee YS, Park SY, Kim JB (2006) Histone deacetylase 1-mediated histone modification regulates osteoblast differentiation. Mol Endocrinol 20(10):2432–2443. https://doi.org/10.1210/me.2006-0061

    Article  PubMed  CAS  Google Scholar 

  58. Schroeder TM, Westendorf JJ (2005) Histone deacetylase inhibitors promote osteoblast maturation. J Bone Miner Res 20(12):2254–2263. https://doi.org/10.1359/JBMR.050813

    Article  PubMed  CAS  Google Scholar 

  59. Goldberg M, Kulkarni AB, Young M, Boskey A (2011) Dentin: structure, composition and mineralization. Front Biosci 3(2):711–35. https://doi.org/10.2741/e281

    Article  Google Scholar 

  60. Narayanan K, Gajjeraman S, Ramachandran A, Hao J, George A (2006) Dentin matrix protein 1 regulates dentin sialophosphoprotein gene transcription during early odontoblast differentiation. J Biol Chem 281(28):19064–19071. https://doi.org/10.1074/jbc.M600714200

    Article  PubMed  CAS  Google Scholar 

  61. Ritchie H (2018) The functional significance of dentin sialoprotein-phosphophoryn and dentin sialoprotein. Int J Oral Sci 10(4):1–6. https://doi.org/10.1038/s41368-018-0035-9

    Article  MathSciNet  CAS  Google Scholar 

  62. Shen L, Xiao Y, Wu Q, Liu L, Zhang C, Pan X (2019) TLR4/NF-ΚB axis signaling pathway-dependent up-regulation of miR-625-5p contributes to human intervertebral disc degeneration by targeting COL1A1. Am J Transl Res 11(3):1374–1388

    PubMed  PubMed Central  CAS  Google Scholar 

  63. Seet LF, Toh LZ, Finger SN, Chu SWL, Stefanovic B, Wong TT (2016) Valproic acid suppresses collagen by selective regulation of Smads in conjunctival fibrosis. J Mol Med 94(3):321–334. https://doi.org/10.1007/s00109-015-1358-z

    Article  PubMed  CAS  Google Scholar 

  64. Van Beneden K, Geers C, Pauwels M, Mannaerts I, Wissing KM, Van Den Branden C et al (2013) Comparison of trichostatin A and valproic acid treatment regimens in a mouse model of kidney fibrosis. Toxicol Appl Pharmacol 271(2):276–284. https://doi.org/10.1016/j.taap.2013.05.013

    Article  PubMed  CAS  Google Scholar 

  65. Chung YL, Wang AJ, Yao LF (2004) Antitumor histone deacetylase inhibitors suppress cutaneous radiation syndrome: implications for increasing therapeutic gain in cancer radiotherapy. Mol Cancer Ther 3(3):317–325

    Article  PubMed  CAS  Google Scholar 

  66. Lee SH, Zahoor M, Hwang JK, Min DS, Choi KY (2012) Valproic Acid Induces Cutaneous Wound Healing In Vivo and Enhances Keratinocyte Motility. PLoS ONE 7(11):1–10. https://doi.org/10.1371/journal.pone.0048791

    Article  CAS  Google Scholar 

  67. Huber LC, Distler JH, Moritz F, Hemmatazad H, Hauser T, Michel BA, Gay RE, Matucci-Cerinic M, Gay S, Distler O, Jüngel A (2007) Trichostatin A prevents the accumulation of extracellular matrix in a mouse model of bleomycin-induced skin fibrosis. Arthritis Rheum 56(8):2755–2764. https://doi.org/10.1002/art.22759

    Article  PubMed  CAS  Google Scholar 

  68. Raicevic G, Najar M, Pieters K, De Bruyn C, Meuleman N, Bron D et al (2012) Inflammation and toll-like receptor ligation differentially affect the osteogenic potential of human mesenchymal stromal cells depending on their tissue origin. Tissue Eng - Part A 18(13–14):1410–1418. https://doi.org/10.1089/ten.TEA.2011.0434

    Article  PubMed  CAS  Google Scholar 

  69. Cho HH, Park HT, Kim YJ, Bae YC, Suh KT, Jung JS (2005) Induction of osteogenic differentiation of human mesenchymal stem cells by histone deacetylase inhibitors. J Cell Biochem 96(3):533–542. https://doi.org/10.1002/jcb.20544

    Article  PubMed  CAS  Google Scholar 

  70. Yuan H, Zhao H, Wang J, Zhang H, Hong L, Li H et al (2019) MicroRNA let-7c-5p promotes osteogenic differentiation of dental pulp stem cells by inhibiting lipopolysaccharide-induced inflammation via HMGA2/PI3K/Akt signal blockade. Clin Exp Pharmacol Physiol 46(4):389–397. https://doi.org/10.1111/1440-1681.13059

    Article  PubMed  CAS  Google Scholar 

  71. Albiero ML, Amorim BR, Martins L, Casati MZ, Sallum EA, Nociti FH et al (2015) Exposure of periodontal ligament progenitor cells to lipopolysaccharide from escherichia coli changes osteoblast differentiation pattern. J Appl Oral Sci 23(2):145–152. https://doi.org/10.1590/1678-775720140334

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  72. Huang Y, Jiang H, Gong Q, Li X, Ling J (2015) Lipopolysaccharide stimulation improves the odontoblastic differentiation of human dental pulp cells. Mol Med Rep 11(5):3547–3552. https://doi.org/10.3892/mmr.2014.3120

    Article  PubMed  CAS  Google Scholar 

  73. He W, Wang Z, Luo Z, Yu Q, Jiang Y, Zhang Y et al (2015) LPS Promote the odontoblastic differentiation of human dental pulp stem cells via MAPK signaling pathway. J Cell Physiol 230(3):554–561. https://doi.org/10.1002/jcp.24732

    Article  PubMed  CAS  Google Scholar 

  74. Mutoh N, Tani-Ishii N, Tsukinoki K, Chieda K, Watanabe K (2007) Expression of Toll-like receptor 2 and 4 in dental pulp. J Endod 33(10):1183–1186. https://doi.org/10.1016/j.joen.2007.05.018

    Article  PubMed  Google Scholar 

  75. Keller JF, Carrouel F, Colomb E, Durand SH, Baudouin C, Msika P et al (2010) Toll-like receptor 2 activation by lipoteichoic acid induces differential production of pro-inflammatory cytokines in human odontoblasts, dental pulp fibroblasts and immature dendritic cells. Immunobiology 215(1):53–59. https://doi.org/10.1016/j.imbio.2009.01.009

    Article  PubMed  CAS  Google Scholar 

  76. Widbiller M, Eidt A, Wölflick M, Lindner SR, Schweikl H, Hiller KA et al (2018) Interactive effects of LPS and dentine matrix proteins on human dental pulp stem cells. Int Endod J 51(8):877–888. https://doi.org/10.1111/iej.12897

    Article  PubMed  CAS  Google Scholar 

  77. Pevsner-Fischer M, Morad V, Cohen-Sfady M, Rousso-Noori L, Zanin-Zhorov A, Cohen S et al (2007) Toll-like receptors and their ligands control mesenchymal stem cell functions. Blood 109(4):1422–1432. https://doi.org/10.1182/blood-2006-06-028704

    Article  PubMed  CAS  Google Scholar 

  78. Li C, Li B, Dong Z, Gao L, He X, Liao L et al (2014) Lipopolysaccharide differentially affects the osteogenic differentiation of periodontal ligament stem cells and bone marrow mesenchymal stem cells through Toll-like receptor 4 mediated nuclear factor κb pathway. Stem Cell Res Ther 5(3):1–13. https://doi.org/10.1186/scrt456

    Article  CAS  Google Scholar 

  79. Liu Y, Gan L, Cui D-X, Yu S-H, Pan Y, Zheng L-W et al (2021) Epigenetic regulation of dental pulp stem cells and its potential in regenerative endodontics. World J Stem Cells 13(11):1647–1666. https://doi.org/10.4252/wjsc.v13.i11.1647

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

The authors are tremendously grateful to Mrs. Diana Lalaouni for her extensive work and efforts in the experimental laboratory stage of the study.

Funding

This project was funded and carried out at the laboratories of the conservative dentistry and periodontology department, Center of Dento-Maxillo-Facial Medicine, Faculty of Medicine, University of Bonn, Germany.

Author information

Author notes

  1. Søren Jepsen and Jochen Winter have equally contributed to this work.

Authors and Affiliations

  1. Department of Endodontics, Faculty of Dentistry, Ain Shams University, Cairo, Egypt

    Sarah Hossam Fahmy

  2. Department of Periodontology, Operative and Preventive Dentistry, Center of Dento-Maxillo-Facial Medicine, Faculty of Medicine, University of Bonn, University Hospital of Bonn, Bonn, Germany

    Sarah Hossam Fahmy, Holger Jungbluth, Søren Jepsen & Jochen Winter

Authors
  1. Sarah Hossam Fahmy
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  2. Holger Jungbluth
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  3. Søren Jepsen
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  4. Jochen Winter
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Contributions

Dr. Sarah Fahmy and Prof Jochen Winter: conceptualization, investigation, and writing original draft; Dr Holger Jungbluth: investigation, and ethical formalities. Prof Soeren Jepsen: supervision and formal analysis. All authors reviewed the editing, gave their final approval, and agreed to be accountable for all aspects of the work.

Corresponding author

Correspondence to Sarah Hossam Fahmy.

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Ethical approval and consent to participate

Procedures followed a protocol approved by the ethical board of the medical faculty, University of Bonn (#217/16). All patients had signed a letter of informed consent.

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The authors declare no competing interests.

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Fahmy, S.H., Jungbluth, H., Jepsen, S. et al. Effects of histone acetyltransferase (HAT) and histone deacetylase (HDAC) inhibitors on proliferative, differentiative, and regenerative functions of Toll-like receptor 2 (TLR-2)-stimulated human dental pulp cells (hDPCs). Clin Oral Invest 28, 53 (2024). https://doi.org/10.1007/s00784-023-05466-5

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