Skip to content
2000
Volume 20, Issue 4
  • ISSN: 1574-888X
  • E-ISSN: 2212-3946

Abstract

Objective

Complications arising from diabetes can result in stem cell dysfunction, impairing their ability to undergo differentiation into various cellular lineages. The present study evaluated the effect of histone deacetylase inhibitors, Valproic acid and Trichostatin A, on the odontogenic differentiation potential of dental pulp stem cells under hyperglycemic conditions.

Methods

Streptozotocin (STZ) induced diabetes mellitus in 12 male Wistar rats. Dental parameters were examined using micro-computed tomography. The odontogenic potential of human pulp stem cells exposed to 30 mM glucose was assessed through alkaline phosphatase assays, examination of gene expression for dentin matrix protein 1 and dentin sialoprotein using real-time PCR, and alizarin red staining for calcium deposition.

Results

Along with reduced dentin thickness and root length in diabetic rats, the results revealed a significant increase in histone deacetylase 3 and 2 gene expressions in isolated diabetic pulp tissues compared to the control groups. The gene expression of odontogenic-related markers and alkaline phosphatase activity in human cultured pulp stem cells under hyperglycemic conditions significantly decreased. Adding Valproic acid and Trichostatin A restored the odontogenic differentiation markers, including calcium deposition, gene expression of dentin sialophosphoprotein, dentin matrix protein 1, and alkaline phosphatase activity.

Conclusion

The data suggests that hyperglycemic conditions negatively impact the odontogenic potential of pulp mesenchymal stem cells. However, histone deacetylase inhibitors improve the impaired odontogenic differentiation capacity. This study implies that histone deacetylases may represent a potential therapeutic target for enhancing the regenerative mineralization of pulp cells in diabetic patients.

© 2025 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/cscr/10.2174/011574888X309466240429051314
2024-05-06
2025-11-01

  • From This Site

    /content/journals/cscr/10.2174/011574888X309466240429051314
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. SinghR. KaurN. KishoreL. Kumar GuptaG. Management of diabetic complications: A chemical constituents based approach.J. Ethnopharmacol.20131501517010.1016/j.jep.2013.08.05124041460
     [Google Scholar]
  2. ClaudinoM. NunesI.S. GennaroG. CestariT.M. SpadellaC.T. GarletG.P. de AssisG.F. Diabetes triggers the loss of tooth structure associated to radiographical and histological dental changes and its evolution to progressive pulp and periapical lesions in rats.Arch. Oral Biol.201560111690169810.1016/j.archoralbio.2015.08.01526355529
     [Google Scholar]
  3. InagakiY. YoshidaK. OhbaH. SetoH. KidoJ. HanejiT. NagataT. High glucose levels increase osteopontin production and pathologic calcification in rat dental pulp tissues.J. Endod.20103661014102010.1016/j.joen.2010.03.01820478457
     [Google Scholar]
  4. MahmoudM. Abu-ShahbaN. AzmyO. El-BadriN. Impact of diabetes mellitus on human mesenchymal stromal cell biology and functionality: Implications for autologous transplantation.Stem Cell Rev.201915219421710.1007/s12015‑018‑9869‑y30680660
     [Google Scholar]
  5. FilionT.M. SkellyJ.D. HuangH. GreinerD.L. AyersD.C. SongJ. Impaired osteogenesis of T1DM bone marrow-derived stromal cells and periosteum-derived cells and their differential in-vitro responses to growth factor rescue.Stem Cell Res. Ther.2017816510.1186/s13287‑017‑0521‑628283030
     [Google Scholar]
  6. GarberS.E. ShabahangS. EscherA.P. TorabinejadM. The effect of hyperglycemia on pulpal healing in rats.J. Endod.2009351606210.1016/j.joen.2008.09.01019084126
     [Google Scholar]
  7. HodjatM. RahmaniS. KhanF. NiazK. Navaei-NigjehM. Mohammadi NejadS. AbdollahiM. Environmental toxicants, incidence of degenerative diseases, and therapies from the epigenetic point of view.Arch. Toxicol.20179172577259710.1007/s00204‑017‑1979‑928516248
     [Google Scholar]
  8. Alvarado-CruzI. Alegría-TorresJ.A. Montes-CastroN. Jiménez- GarzaO. Quintanilla-VegaB. Environmental epigenetic changes, as risk factors for the development of diseases in children: A systematic review.Ann. Glob. Health201884221222410.29024/aogh.90930873799
     [Google Scholar]
  9. LiuZ. ChenT. SunW. YuanZ. YuM. ChenG. GuoW. XiaoJ. TianW. DNA demethylation rescues the impaired osteogenic differentiation ability of human periodontal ligament stem cells in high glucose.Sci. Rep.2016612744710.1038/srep2744727273319
     [Google Scholar]
  10. ChenA.C.H. HuangW. FongS.W. ChanC. LeeK.C. YeungW.S.B. LeeY.L. Hyperglycemia altered DNA methylation status and impaired pancreatic differentiation from embryonic stem cells.Int. J. Mol. Sci.202122191072910.3390/ijms22191072934639069
     [Google Scholar]
  11. VermaP.R. ItankarP.R. AroraS.K. Evaluation of antidiabetic antihyperlipidemic and pancreatic regeneration, potential of aerial parts of Clitoria ternatea.Rev. Bras. Farmacogn.201323581982910.1590/S0102‑695X2013000500015
     [Google Scholar]
  12. Kalbasi AnarakiP. PateckiM. LarmannJ. TkachukS. JurkK. HallerH. TheilmeierG. DumlerI. Urokinase receptor mediates osteogenic differentiation of mesenchymal stem cells and vascular calcification via the complement C5a receptor.Stem Cells Dev.201423435236210.1089/scd.2013.031824192237
     [Google Scholar]
  13. GurvichN. TsygankovaO.M. MeinkothJ.L. KleinP.S. Histone deacetylase is a target of valproic acid-mediated cellular differentiation.Cancer Res.20046431079108610.1158/0008‑5472.CAN‑03‑079914871841
     [Google Scholar]
  14. HuumonenS. TjäderhaneL. LarmasM. Greater concentration of dietary sucrose decreases dentin formation and increases the area of dentinal caries in growing rats.J. Nutr.1997127112226223010.1093/jn/127.11.22269349851
     [Google Scholar]
  15. AbbassyM.A. WatariI. BakryA.S. HambaH. HassanA.H. TagamiJ. OnoT. Diabetes detrimental effects on enamel and dentine formation.J. Dent.201543558959610.1016/j.jdent.2015.01.00525681642
     [Google Scholar]
  16. GutowskaI. Baranowska-BosiackaI. RybickaM. NoceńI. DudzińskaW. MarchlewiczM. WiszniewskaB. ChlubekD. Changes in the concentration of microelements in the teeth of rats in the final stage of type 1 diabetes, with an absolute lack of insulin.Biol. Trace Elem. Res.2011139333234010.1007/s12011‑010‑8666‑520336494
     [Google Scholar]
  17. WangJ. WangB. LiY. WangD. LinglingE. BaiY. LiuH. High glucose inhibits osteogenic differentiation through the BMP signaling pathway in bone mesenchymal stem cells in mice.EXCLI J.20131258459727103890
     [Google Scholar]
  18. CaoB. LiuN. WangW. High glucose prevents osteogenic differentiation of mesenchymal stem cells via lncRNA AK028326/CXCL13 pathway.Biomed. Pharmacother.20168454455110.1016/j.biopha.2016.09.05827693963
     [Google Scholar]
  19. DrawnelF.M. BoccardoS. PrummerM. DelobelF. GraffA. WeberM. GérardR. BadiL. Kam-ThongT. BuL. JiangX. HoflackJ.C. KiialainenA. JeworutzkiE. AoyamaN. CarlsonC. BurcinM. GromoG. BoehringerM. StahlbergH. HallB.J. MagnoneM.C. KolajaK. ChienK.R. BaillyJ. IaconeR. Disease modeling and phenotypic drug screening for diabetic cardiomyopathy using human induced pluripotent stem cells.Cell Rep.20149381082010.1016/j.celrep.2014.09.05525437537
     [Google Scholar]
  20. YamauchiY. CooperP.R. ShimizuE. KobayashiY. SmithA.J. DuncanH.F. Histone acetylation as a regenerative target in the dentine-pulp complex.Front. Genet.202011110.3389/fgene.2020.0000132117431
     [Google Scholar]
  21. JanczuraK.J. VolmarC.H. SartorG.C. RaoS.J. RicciardiN.R. LambertG. BrothersS.P. WahlestedtC. Inhibition of HDAC3 reverses Alzheimer’s disease-related pathologies in vitro and in the 3xTg-AD mouse model.Proc. Natl. Acad. Sci.201811547E11148E1115710.1073/pnas.180543611530397132
     [Google Scholar]
  22. LiaoY. ChengJ. KongX. LiS. LiX. ZhangM. ZhangH. YangT. DongY. LiJ. XuY. YuanZ. HDAC3 inhibition ameliorates ischemia/reperfusion-induced brain injury by regulating the microglial cGAS-STING pathway.Theranostics202010219644966210.7150/thno.4765132863951
     [Google Scholar]
  23. SanaeiM KavoosiF. Effect of trichostatin a on histone deacetylases 1, 2 and 3, p21Cip1/Waf1/Sdi1, p27Kip1, and p57Kip2 gene expression in breast cancer sk-br-3 cell line.Asian Pac. J. Cancer Biol.2020525762
     [Google Scholar]
  24. KawagoeR. KawagoeH. SanoK. Valproic acid induces apoptosis in human leukemia cells by stimulating both caspase-dependent and -independent apoptotic signaling pathways.Leuk. Res.200226549550210.1016/S0145‑2126(01)00151‑511916526
     [Google Scholar]
  25. PainoF. NoceM. TirinoV. NaddeoP. DesiderioV. PirozziG. RosaA. LainoL. AltucciL. PapaccioG. Histone deacetylase inhibition with valproic acid downregulates osteocalcin gene expression in human dental pulp stem cells and osteoblasts: Evidence for HDAC2 involvement.Stem Cells201432127928910.1002/stem.154424105979
     [Google Scholar]
  26. DuncanH.F. SmithA.J. FlemingG.J.P. CooperP.R. Histone deacetylase inhibitors epigenetically promote reparative events in primary dental pulp cells.Exp. Cell Res.2013319101534154310.1016/j.yexcr.2013.02.02223562654
     [Google Scholar]
  27. DuncanH.F. SmithA.J. FlemingG.J.P. CooperP.R. Histone deacetylase inhibitors induced differentiation and accelerated mineralization of pulp-derived cells.J. Endod.201238333934510.1016/j.joen.2011.12.01422341071
     [Google Scholar]
  28. HuynhN.C.N. EvertsV. AmpornaramvethR.S. Histone deacetylases and their roles in mineralized tissue regeneration.Bone Rep.20177334010.1016/j.bonr.2017.08.00128856178
     [Google Scholar]
  29. JinH. ParkJ.Y. ChoiH. ChoungP.H. HDAC inhibitor trichostatin A promotes proliferation and odontoblast differentiation of human dental pulp stem cells.Tissue Eng. Part A2013195-661362410.1089/ten.tea.2012.016323013422
     [Google Scholar]
/content/journals/cscr/10.2174/011574888X309466240429051314
Loading
Histone Deacetylase Inhibitors Restore the Odontogenic Differentiation Potential of Dental Pulp Stem Cells under Hyperglycemic Conditions
Curr Stem Cell Res Ther 20, 441 (2025); https://doi.org/10.2174/011574888X309466240429051314
/content/journals/cscr/10.2174/011574888X309466240429051314
/content/journals/cscr/10.2174/011574888X309466240429051314
Loading

Data & Media loading...


  • Article Type:     Research Article
Keyword(s): chronic hyperglycemia; dentin; Diabetes mellitus; histone deacetylase inhibitors; mesenchymal stem cells; odontogenic differentiation

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test