Efecto de la N-acetilcisteína sobre la diferenciación a linaje odontoblástico de microesferas de células madre de pulpa dental

Antecedentes: La N-acetilcisteína (NAC), profármaco de cisteína y precursor del glutatión (GSH), presenta propiedades antimicrobianas, descomponiendo biopelículas de patógenos orales. Su actividad antioxidante y antiinflamatoria inhibe la señalización de NF-κB y la expresión de citoquinas proinflama...

Full description

Autores:: Araque Acosta, Yalnia Andrea
Gómez Mosquera, Paula Andrea
Useche Rodríguez, Paula Andrea

Tipo de recurso:: https://purl.org/coar/resource_type/c_7a1f

Fecha de publicación:: 2025

Institución:: Universidad El Bosque

Repositorio:: Repositorio U. El Bosque

Idioma:: spa

id	UNBOSQUE2_28c3cb41fac875d421141e3e6df3e639
oai_identifier_str	oai:repositorio.unbosque.edu.co:20.500.12495/15695
network_acronym_str	UNBOSQUE2
network_name_str	Repositorio U. El Bosque
repository_id_str
dc.title.none.fl_str_mv	Efecto de la N-acetilcisteína sobre la diferenciación a linaje odontoblástico de microesferas de células madre de pulpa dental
dc.title.translated.none.fl_str_mv	Effect of N -acetylcysteine on the differentiation of dental pulp stem cell microspheres into odontoblast lineage
title	Efecto de la N-acetilcisteína sobre la diferenciación a linaje odontoblástico de microesferas de células madre de pulpa dental
spellingShingle	Efecto de la N-acetilcisteína sobre la diferenciación a linaje odontoblástico de microesferas de células madre de pulpa dental N-Acetilcisteína Células madre mesenquimales Diferenciación celular Terapia pulpar vital Odontoblasto N- Acetylcysteine Mesenchymal stem cells Cells differentiation Vital pulp therapy Odontoblast WU 230
title_short	Efecto de la N-acetilcisteína sobre la diferenciación a linaje odontoblástico de microesferas de células madre de pulpa dental
title_full	Efecto de la N-acetilcisteína sobre la diferenciación a linaje odontoblástico de microesferas de células madre de pulpa dental
title_fullStr	Efecto de la N-acetilcisteína sobre la diferenciación a linaje odontoblástico de microesferas de células madre de pulpa dental
title_full_unstemmed	Efecto de la N-acetilcisteína sobre la diferenciación a linaje odontoblástico de microesferas de células madre de pulpa dental
title_sort	Efecto de la N-acetilcisteína sobre la diferenciación a linaje odontoblástico de microesferas de células madre de pulpa dental
dc.creator.fl_str_mv	Araque Acosta, Yalnia Andrea Gómez Mosquera, Paula Andrea Useche Rodríguez, Paula Andrea
dc.contributor.advisor.none.fl_str_mv	Jiménez Ortegón, Nury Tatiana Perdomo Lara, Sandra Castaño Duque, Sandra Patricia
dc.contributor.author.none.fl_str_mv	Araque Acosta, Yalnia Andrea Gómez Mosquera, Paula Andrea Useche Rodríguez, Paula Andrea
dc.subject.none.fl_str_mv	N-Acetilcisteína Células madre mesenquimales Diferenciación celular Terapia pulpar vital Odontoblasto
topic	N-Acetilcisteína Células madre mesenquimales Diferenciación celular Terapia pulpar vital Odontoblasto N- Acetylcysteine Mesenchymal stem cells Cells differentiation Vital pulp therapy Odontoblast WU 230
dc.subject.keywords.none.fl_str_mv	N- Acetylcysteine Mesenchymal stem cells Cells differentiation Vital pulp therapy Odontoblast
dc.subject.nlm.none.fl_str_mv	WU 230
description	Antecedentes: La N-acetilcisteína (NAC), profármaco de cisteína y precursor del glutatión (GSH), presenta propiedades antimicrobianas, descomponiendo biopelículas de patógenos orales. Su actividad antioxidante y antiinflamatoria inhibe la señalización de NF-κB y la expresión de citoquinas proinflamatorias como IL-1β, IL-6, IL-8 y factor de necrosis tumoral alfa (TNF-α). Por esta razón, la NAC podría tener potencial como agente terapéutico en la terapia de pulpa vital Objetivo: Evaluar el efecto de la NAC sobre la diferenciación de las células madre de pulpa dental humana en esferoides a linaje odontoblastoide. Materiales y Métodos: Sé cultivaron DPSCs en monocapa y se generaron esferoides 3D en placas no adhesivas, en condiciones estándar de cultivo. Los esferoides fueron caracterizados morfológicamente a las 72 horas mediante microscopio óptico y el software AnaSP2 para evaluar parámetros como convexidad, diámetro y esfericidad. Para la diferenciación odontoblastoide se empleó NAC a 1.83mM, se evaluó a los 7,14. la expresión génica de Fosfatasa alcalina (ALP), RUNX2, Sialoproteína dentinal y Fosfoproteína dentinal realizando RTqPCR empleando la fórmula doble delta CT (2ΔΔCt). Resultados: Las células madre de pulpa dental (DPSCs) formaron esferoides tridimensionales homogéneos y de morfología regular a las 72 h bajo condiciones de baja adherencia. El análisis morfológico reveló mejoras progresivas en convexidad, solidez y esfericidad en los esferoides tratados con N-acetilcisteína (NAC, 1.83 mM), destacando una morfología más compacta y simétrica a los 14 días. A nivel molecular, el tratamiento con NAC promovió significativamente la expresión de genes odontoblastoides (Col1a1, RUNX2, OCN, DSPP, DMP1), superando al control positivo en varios marcadores, lo que evidencia su efecto potenciador en la diferenciación celular. Conclusiones: La NAC (1.83 mM) mejoró la morfología de esferoides de DPSCs y aumentó la expresión de genes odontogénicos, superando al medio convencional, lo que respalda su potencial en terapia pulpar vital.
publishDate	2025
dc.date.accessioned.none.fl_str_mv	2025-08-11T20:36:32Z
dc.date.available.none.fl_str_mv	2025-08-11T20:36:32Z
dc.date.issued.none.fl_str_mv	2025-07
dc.type.coar.fl_str_mv	http://purl.org/coar/resource_type/c_7a1f
dc.type.local.spa.fl_str_mv	Tesis/Trabajo de grado - Monografía - Especialización
dc.type.coar.none.fl_str_mv	https://purl.org/coar/resource_type/c_7a1f
dc.type.driver.none.fl_str_mv	info:eu-repo/semantics/bachelorThesis
dc.type.coarversion.none.fl_str_mv	https://purl.org/coar/version/c_970fb48d4fbd8a85
format	https://purl.org/coar/resource_type/c_7a1f
dc.identifier.uri.none.fl_str_mv	https://hdl.handle.net/20.500.12495/15695
dc.identifier.instname.spa.fl_str_mv	instname:Universidad El Bosque
dc.identifier.reponame.spa.fl_str_mv	reponame:Repositorio Institucional Universidad El Bosque
dc.identifier.repourl.none.fl_str_mv	repourl:https://repositorio.unbosque.edu.co
url	https://hdl.handle.net/20.500.12495/15695
identifier_str_mv	instname:Universidad El Bosque reponame:Repositorio Institucional Universidad El Bosque repourl:https://repositorio.unbosque.edu.co
dc.language.iso.fl_str_mv	spa
language	spa
dc.relation.references.none.fl_str_mv	1. K. R. Atkuri, J. J. Mantovani, L. A. Herzenberg, and L. A. Herzenberg, “N-Acetylcysteine–a safe antidote for cysteine/ glutathione deficiency,” Current Opinion in Pharmacology, vol. 7, no. 4, pp. 355–359, 2007. 2. Sahasrabudhe SA, Terluk MR, Kartha RV. N-acetylcysteine Pharmacology and Applications in Rare Diseases—Repurposing an Old Antioxidant. Antioxidants [Internet]. 2023 Jun 21;12(7) 1316. 3. Pei Y, Liu H, Yang Y, Jiao Y, Tay FR, Chen J. Biological activities and potential oral applications of N-acetylcysteine: progress and prospects. Oxid Med Cell Longev. 2018;2018:2835787. doi:10.1155/2018/2835787. 4. Duncan HF. Present status and future directions-Vital pulp treatment and pulp preservation strategies. Int Endod J. 2022 May;55 Suppl 3(Suppl 3):497-511. doi: 10.1111/iej.13688. Epub 2022 Feb 3. PMID: 35080024; PMCID: PMC9306596. 5. Duncan HF, Cooper PR., P.R. (2020) Pulp innate immune defense: translational opportunities. Journal of Endodontics, 46, S10–S18. 6. Duncan, H.F., Chong, B.S., Del Fabbro, M., El-Karim, I., Galler, K., Kirkevang, L.L. et al. (2021a) The development of European Society of Endodontology S3-level guidelines for the treatment of pulpal and apical disease. International Endodontic Journal, 54, 643–645. 7. Asgary, S., Eghbal, M.J., Fazlyab, M., Baghban, A.A. & Ghoddusi, J. (2015) Five-year results of vital pulp therapy in permanent mo-lars with irreversible pulpitis: a non-inferiority multicenter ran-domized clinical trial. Clinical Oral Investigations, 19, 335–341. 8. Arora, S., Cooper, P.R., Friedlander, L.T., Rizwan, S., Seo, B., Rich, A.M. et al. (2021) Potential application of immunotherapy for modulation of pulp inflammation: opportunities for vital pulp treatment. International Endodontic Journal, 54, 1263–1274. 9. Cui X, Hartanto Y, Zhang H. 2017 Advances in multicellular spheroids formation. J. R. Soc. Interface 14: 20160877. http://dx.doi.org/10.1098/rsif.2016.0877 10. Y J, Ln N, S M, J L, Fr T, Jh C. Quaternary ammonium-based biomedical materials: State-of-the-art, toxicological aspects and antimicrobial resistance [Internet]. Progress in polymer science. 2017. 11. Hahn CL, Liewehr FR. Innate Immune Responses of the Dental Pulp to Caries. Journal of Endodontics. 2007 Jun;33(6):643–51. 12. Zheng H, Liu J, Sun L, Meng Z. The role of N-acetylcysteine in osteogenic microenvironment for bone tissue engineering. Front Cell Dev Biol. 2024 Jul 11;12:1435125. doi:10.3389/fcell.2024.1435125. PMID: 39055649; PMCID: PMC11269162. 13. Charoenpong H, Osathanon T, Pavasant P, Limjeerajarus N, Keawprachum B, Limjeerajarus CN, et al. Mechanical stress induced S100A7 expression in human dental pulp cells to augment osteoclast differentiation. Oral Diseases. 2019 Jan 25;25(3):812–21. 14. Koh AS, Simmons-Willis TA, Pritchard JB, Grassl SM, Ballatori N. Identification of a Mechanism by Which the Methylmercury Antidotes N-Acetylcysteine and Dimercaptopropanesulfonate Enhance Urinary Metal Excretion: Transport by the Renal Organic Anion Transporter-1. Molecular Pharmacology. 2002 oct1;62(4):921–6. 15. Bjørndal L, Mjör IA. Pulp-dentin biology in restorative dentistry. Part 4: Dental caries--characteristics of lesions and pulpal reactions. Quintessence International (Berlin, Germany: 1985) [Internet]. 2001 Oct 1;32(9):717–36. 16. Yu J, Deng Z, Shi J, Zhai H, Nie X, Zhuang H, et al. Differentiation of Dental Pulp Stem Cells into Regular-Shaped Dentin-Pulp Complex Induced by Tooth Germ Cell Conditioned Medium. Tissue Engineering. 2006 Nov;12(11):3097–105. 17. Hybertson BM, Gao B, Bose SK, McCord JM. Oxidative stress in health and disease: the therapeutic potential of Nrf2 activation. Molecular Aspects of Medicine [Internet]. 2011 Aug 1;32(4-6):234–46. 18. J. H. Jun, S. H. Lee, H. B. Kwak et al., “N-Acetylcysteine stimulates osteoblastic differentiation of mouse calvarial cells,” Journal of Cellular Biochemistry, vol. 103, no. 4, pp. 1246–1255, 2008. 19. F. Pajonk, K. Riess, A. Sommer, and W. H. McBride, “N-Acetyl-L-cysteine inhibits 26S proteasome function: implications for effects on NF-κB activation,” Free Radical Biology & Medicine, vol. 32, no. 6, pp. 536–543, 2002. 20. H. Kim, J. Y. Seo, K. H. Roh, J. W. Lim, and K. H. Kim, “Suppression of NF-κB activation and cytokine production by N-acetylcysteine in pancreatic acinar cells,” Free Radical Biology & Medicine, vol. 29, no. 7, pp. 674–683, 2000. 21. S. P. Karapinar, Y. Z. A. Ulum, B. Ozcelik et al., “The effect of N-acetylcysteine and calcium hydroxide on TNF-α and TGF- β1 in lipopolysaccharide-activated macrophages,” Archives ofOral Biology, vol. 68, pp. 48–54, 2016. 22. D. Y. Kim, J. H. Jun, H. L. Lee et al., “N-Acetylcysteine prevents LPS-induced pro-inflammatory cytokines and MMP2 production in gingival fibroblasts,” Archives of PharmacalResearch, vol. 30, no. 10, pp. 1283–1292, 2007. 23. N. Celik, S. Askın, M. A. Gul, and N. Seven, “The effect of restorative materials on cytokines in gingival crevicular fluid,” Archives of Oral Biology, vol. 84, pp. 139–144, 2017. 24. Achilli T-M, Meyer J, Morgan JR. 2012 Advances in the formation, use and understanding of multi-cellular spheroids. Expert Opin Biol. Ther. 12, 1347– 1360. (doi:10.1517/14712598.2012.707181) 25. J. H. Moon, Y. S. Choi, H. W. Lee, J. S. Heo, S. W. Chang, and J. Y. Lee, “Antibacterial effects of N-acetylcysteine against endodontic pathogens,” Journal of Microbiology, vol. 54, no. 4, pp. 322–329, 2016. 26. S. De Flora, A. Izzotti, F. D'Agostini, and R. M. Balansky, “Mechanisms of N-acetylcysteine in the prevention of DNA damage and cancer, with special reference to smokingrelated end-points,” Carcinogenesis, vol. 22, no. 7, pp. 999– 1013, 2001. 27. Baker, B.M.,y Chen, C.S. (2012). Deconstructing the third dimension: how 3D culture microenvironments alter cellular cues. J. Cell Sci., 125: 3015-3024. 28. Meseguer J, Esteban Abad M de los Á, Mulero Méndez VF, Cuesta Peñafiel A, Sepulcre Cortés MP. Esferoides y esferas líquidas: Cultivos celulares en 3D para mimetizar el ambiente de las células en el organismo. Eubacteria. 2015;(34):2015. 29. Choi J, Kim D, Kim M, Kim S, Kim J, Choi Y. Outcomes of direct pulp-capping procedures performed by dental students: A retrospective study. J Am Dent Assoc. 2006;137(12):1699-705. 30. Asgary S, Nazarian H, Khojasteh A, Shokouhinejad N. Gene expression and cytokine release during odontogenic differentiation of human dental pulp stem cells induced by 2 endodontic biomaterials. J Endod 2014;40:387-392 31. Paranjpe A, Sung EC, Cacalano NA, Hume WR, Jewett A. N-acetylcysteine protects pulp cells from resin toxins in vivo. J Dent Res. 2008;87(6):537–541. doi:10.1177/154405910808700603. 32. Diamanti E, Mathieu S, Jeanneau C, et al. Endoplasmic reticulum stress and mineralization inhibition mechanism by the resinous monomer HEMA. Int Endod J 2013;46:160–8. 33. Lin RZ, Chang HY. Recent advances in three-dimensional multicellular spheroid culture for biomedical research. Biotechnol J. 2008 Oct;3(9-10):1172-84. doi: 10.1002/biot.200700228. Erratum in: Biotechnol J. 2008 Oct;3(9-10):1285. Lin, Ruei-Zhen [corrected to Lin, Ruei-Zeng]. PMID: 18566957. 34. Min KS, Kwon YY, Lee HJ, et al. Effects of proinflammatory cytokines on the expression of mineralization markers and heme oxygenase-1 in human pulp cells. J Endod 2006;32:39–43. 35.Takeuchi O, Akira S. Pattern recognition receptors and inflammation. Cell 2010; 140:805–20. 36. Margunato S, Tas¸lı PN, Aydın S, et al. In vitro evaluation of ProRoot MTA, Biodentine, and MM-MTA on human alveolar bone marrow stem cells in terms of biocompatibility and mineralization. J Endod 2015;41:1646–52. 37. Bortoluzzi EA, Niu LN, Palani CD, et al. Cytotoxicity and osteogenic potential of silicate calcium cements as potential protective materials for pulpal revascularization. Dent Mater 2015;31:1510–22. 38. Jang JH, Kang M, Ahn S, et al. Tooth discoloration after the use of new pozzolan cement (Endocem) and mineral trioxide aggregate and the effects of internal bleaching. J Endod 2013;39:1598–602 39. Camilleri J., Sorrentino F., Damidot D. Investigation of the hydration and bioactivity of radiopacified tricalcium silicate cement, Biodentine and MTA Angelus. Dental Materials. 2013;29(5):580–593. doi: 10.1016/j.dental.2013.03.007. 40. Grech L., Mallia B., Camilleri J. Investigation of the physical properties of tricalcium silicate cement-based root-end filling materials. Dental Materials. 2013;29(2):e20–e28. doi: 10.1016/j.dental.2012.11.007. 41. Al-Sherbiny I. M., Farid M. H., Abu-Seida A. M., Motawea I. T., Bastawy H. A. Chemico-physical and mechanical evaluation of three calcium silicate-based pulp capping materials. The Saudi Dental Journal. 2020 doi: 10.1016/j.sdentj.2020.02.001 42. Kayahan M. B., Nekoofar M. H., McCann A., et al. Effect of acid etching procedures on the compressive strength of 4 calcium silicate-based endodontic cements. Journal of Endodontia. 2013;39(12):1646–1648. doi: 10.1016/j.joen.2013.09.008. 43. Vallés M., Mercadé M., Duran-Sindreu F., Bourdelande J. L., Roig M. Influence of Light and Oxygen on the Color Stability of Five Calcium Silicate- based Materials. Journal of Endodontia. 2013;39(4):525–528. doi: 10.1016/j.joen.2012.12.021 44. Palma P. J., Marques J. A., Falacho R. I., et al. Six-month color stability assessment of two calcium silicate-based cements used in regenerative endodontic procedures. Journal of Functional BiomaterialsJournal of Functional Biomaterials. 2019;10(1):p. 14. doi: 10.3390/jfb10010014. 45. Duarte M. A. H., Marciano M. A., Vivan R. R., Tanomaru Filho M., Tanomaru J. M. G., Camilleri J. Tricalcium silicate-based cements: properties and modifications. Brazilian Oral Research. 2018;32(Supplement 1):e70–118. doi: 10.1590/1807-3107bor-2018.vol32.0070 46. Akhlaghi N, Khademi A. Outcomes of vital pulp therapy in permanent teeth with different medicaments: a literature review. Iran Endod J. 2015;10(1):6–14. 47. Kearney M, Cooper PR, Smith AJ, Duncan HF. Epigenetic Approaches to the Treatment of Dental Pulp Inflammation and Repair: Opportunities and Obstacles. Front Genet. 2018 Aug 7;9:311. doi: 10.3389/fgene.2018.00311. PMID: 30131827; PMCID: PMC6090030. 48. G. F. Rushworth and I. L. Megson, “Existing and potential therapeutic uses for N-acetylcysteine: the need for conversion to intracellular glutathione for antioxidant benefits,” Pharmacology & Therapeutics, vol. 141, no. 2, pp. 150–159, 2014. 49. Millea PJ. N-acetylcysteine: multiple clinical applications. Am Fam Physician. 2009 Aug 1;80(3):265-9. PMID: 19621836. 50. Shahripour R.B., Harrigan M.R., Alexandrov A.V. N-acetylcysteine (NAC) in neurological disorders: Mechanisms of action and therapeutic opportunities. Brain Behav. 2014;4:108–122. doi: 10.1002/brb3.208 51. Schweikl H, Hartmann A, Hiller KA, Spagnuolo G, Bolay C, Brockhoff G, Schmalz G. Inhibition of TEGDMA and HEMA induced genotoxicity and cell cycle arrest by N acetylcysteine. Dent Mater. 2007 Jun;23(6):688–95. doi:10.1016/j.dental.2006.06.021 52. Pawar M, Pawar V, Thete SG, et al. Enhance-ment of Odontoblastic Differentiation of Stem Cells from Exfoliated Deciduous Tooth Using N-acetylcysteine—An In Vitro Study. J Contemp Dent Pract 2021;22(8):882–889. 53. Piccinini F, Tesei A, Arienti C, Bevilacqua A. AnaSP: a software suite for automatic image analysis of multicellular spheroids. Comput Methods Programs Biomed. 2015;119(1):43–52. 54. Zanoni M, Pignatta S, Arienti C, Bonafè M, Tesei A. Anticancer drug discovery using multicellular tumor spheroid models. Expert Opin Drug Discov. 2019;14(3):289–301. doi:10.1080/17460441.2019.1571130. 55. Gronthos, S., Mankani, M., Brahim, J., Robey, P. G., & Shi, S. (2000). Postnatal human dental pulp stem cells (DPSCs) in vitro and in vivo. Proceedings of the National Academy of Sciences of the United States of America, 97(25), 13625–13630. https://doi.org/10.1073/pnas.240309797 56. Meng Z, Liu J, Feng Z, Guo S, Wang M, Wang Z, et al. N acetylcysteine regulates dental follicle stem cell osteogenesis and alveolar bone repair via ROS scavenging. Stem Cell Res Ther. 2022;13:466. 57. Breslin, S., & O'Driscoll, L. (2013). Three-dimensional cell culture: The missing link in drug discovery. Drug Discovery Today, 18(5–6), 240–249. https://doi.org/10.1016/j.drudis.2012.10.003 58. Ghoddusi J, Forghani M, Parisai I. New approaches in vital pulp therapy in permanent teeth. Iran Endod J. 2013;8(1):6–15. 59. Countryman K, Chen YW, Johnson JD, Paranjpe A. N-acetylcysteine protects the stem cells of the apical papilla. Front Dent Med. 2022;3:848081. doi:10.3389/fdmed.2022.848081
dc.rights.en.fl_str_mv	Attribution-NonCommercial-ShareAlike 4.0 International
dc.rights.coar.fl_str_mv	http://purl.org/coar/access_right/c_abf2
dc.rights.uri.none.fl_str_mv	http://creativecommons.org/licenses/by-nc-sa/4.0/
dc.rights.local.spa.fl_str_mv	Acceso abierto
dc.rights.accessrights.none.fl_str_mv	https://purl.org/coar/access_right/c_abf2
rights_invalid_str_mv	Attribution-NonCommercial-ShareAlike 4.0 International http://creativecommons.org/licenses/by-nc-sa/4.0/ Acceso abierto https://purl.org/coar/access_right/c_abf2 http://purl.org/coar/access_right/c_abf2
dc.format.mimetype.none.fl_str_mv	application/pdf
dc.publisher.program.spa.fl_str_mv	Especialización en endodoncia
dc.publisher.grantor.spa.fl_str_mv	Universidad El Bosque
dc.publisher.faculty.spa.fl_str_mv	Facultad de Odontología
institution	Universidad El Bosque
bitstream.url.fl_str_mv	https://pruebas-update-repositorio-unbosque.cloudbiteca.com/bitstreams/7909bd84-d27b-4a01-8a8a-5c4ccca20c5a/download https://pruebas-update-repositorio-unbosque.cloudbiteca.com/bitstreams/94ecd05e-d657-466b-b34f-60eb7c0e45ee/download https://pruebas-update-repositorio-unbosque.cloudbiteca.com/bitstreams/67bfd8dd-70fe-47a4-8faa-872928852b17/download https://pruebas-update-repositorio-unbosque.cloudbiteca.com/bitstreams/5afdedc5-3d40-44e3-97d8-c676c77e8ad2/download https://pruebas-update-repositorio-unbosque.cloudbiteca.com/bitstreams/0d57d67a-d473-4731-9e17-5dac00d9d8fa/download https://pruebas-update-repositorio-unbosque.cloudbiteca.com/bitstreams/9178a908-68fe-4101-88c4-fb6be986adc2/download https://pruebas-update-repositorio-unbosque.cloudbiteca.com/bitstreams/ea4a7cd3-9bb7-4a88-9e24-b3db7cb891bd/download
bitstream.checksum.fl_str_mv	a26f1bd769f6c595d62a3513d46fb87a 17cc15b951e7cc6b3728a574117320f9 22039ed935b72a3a307053c767754997 6674171e672270513aa8dd573d280be5 5643bfd9bcf29d560eeec56d584edaa9 1ba7d267e69e8dae0cdb9f0a09345f75 d134737a82c561cca33196ccaa3b3aca
bitstream.checksumAlgorithm.fl_str_mv	MD5 MD5 MD5 MD5 MD5 MD5 MD5
repository.name.fl_str_mv	Repositorio Institucional Universidad El Bosque
repository.mail.fl_str_mv	bibliotecas@biteca.com
_version_	1849967229382164480
spelling	Jiménez Ortegón, Nury TatianaPerdomo Lara, SandraCastaño Duque, Sandra PatriciaAraque Acosta, Yalnia AndreaGómez Mosquera, Paula AndreaUseche Rodríguez, Paula Andrea2025-08-11T20:36:32Z2025-08-11T20:36:32Z2025-07https://hdl.handle.net/20.500.12495/15695instname:Universidad El Bosquereponame:Repositorio Institucional Universidad El Bosquerepourl:https://repositorio.unbosque.edu.coAntecedentes: La N-acetilcisteína (NAC), profármaco de cisteína y precursor del glutatión (GSH), presenta propiedades antimicrobianas, descomponiendo biopelículas de patógenos orales. Su actividad antioxidante y antiinflamatoria inhibe la señalización de NF-κB y la expresión de citoquinas proinflamatorias como IL-1β, IL-6, IL-8 y factor de necrosis tumoral alfa (TNF-α). Por esta razón, la NAC podría tener potencial como agente terapéutico en la terapia de pulpa vital Objetivo: Evaluar el efecto de la NAC sobre la diferenciación de las células madre de pulpa dental humana en esferoides a linaje odontoblastoide. Materiales y Métodos: Sé cultivaron DPSCs en monocapa y se generaron esferoides 3D en placas no adhesivas, en condiciones estándar de cultivo. Los esferoides fueron caracterizados morfológicamente a las 72 horas mediante microscopio óptico y el software AnaSP2 para evaluar parámetros como convexidad, diámetro y esfericidad. Para la diferenciación odontoblastoide se empleó NAC a 1.83mM, se evaluó a los 7,14. la expresión génica de Fosfatasa alcalina (ALP), RUNX2, Sialoproteína dentinal y Fosfoproteína dentinal realizando RTqPCR empleando la fórmula doble delta CT (2ΔΔCt). Resultados: Las células madre de pulpa dental (DPSCs) formaron esferoides tridimensionales homogéneos y de morfología regular a las 72 h bajo condiciones de baja adherencia. El análisis morfológico reveló mejoras progresivas en convexidad, solidez y esfericidad en los esferoides tratados con N-acetilcisteína (NAC, 1.83 mM), destacando una morfología más compacta y simétrica a los 14 días. A nivel molecular, el tratamiento con NAC promovió significativamente la expresión de genes odontoblastoides (Col1a1, RUNX2, OCN, DSPP, DMP1), superando al control positivo en varios marcadores, lo que evidencia su efecto potenciador en la diferenciación celular. Conclusiones: La NAC (1.83 mM) mejoró la morfología de esferoides de DPSCs y aumentó la expresión de genes odontogénicos, superando al medio convencional, lo que respalda su potencial en terapia pulpar vital.Grupo de investigación INMUBO - Grupo de Inmunología celular y molecular Universidad El BosqueEspecialista en endodonciaEspecializaciónBackground : N-acetylcysteine (NAC), a prodrug of cysteine and a precursor of glutathione (GSH), exhibits antimicrobial properties by breaking down oral pathogen biofilms. Its antioxidant and anti-inflammatory activity inhibits NF-κB signaling and the expression of proinflammatory cytokines such as IL-1β, IL-6, IL-8, and tumor necrosis factor alpha (TNF-α). For this reason, NAC could have potential as a therapeutic agent in vital pulp therapy. Aim: To evaluate the effect of NAC on the differentiation of human dental pulp stem cells in spheroids to an odontoblastic lineage. Methods: DPSCs were cultured in monolayers, and 3D spheroids were generated in nonadhesive plates under standard culture conditions. The spheroids were morphologically characterized at 72 hours using an optical microscope and AnaSP2 software to evaluate parameters such as convexity, diameter, and sphericity. For odontoblastic differentiation, NAC at 1.83 mM was used, and the gene expression of alkaline phosphatase (ALP), RUNX2, dentin sialoprotein, and dentin phosphoprotein was evaluated at 7 and 14 days by RTqPCR using the double delta CT (2ΔΔCt) formula. Results: Dental pulp stem cells (DPSCs) formed homogeneous three-dimensional spheroids with regular morphology at 72 h under low-adhesion conditions. Morphological analysis revealed progressive improvements in convexity, solidity, and sphericity in spheroids treated with N-acetylcysteine (NAC, 1.83 mM), highlighting a more compact and symmetrical morphology at 14 days. At the molecular level, treatment with NAC significantly promoted the expression of odontoblastic genes (Col1a1, RUNX2, OCN, DSPP, DMP1), surpassing the positive control in several markers, which demonstrates its enhancing effect on cell differentiation. Conclusions: NAC (1.83 mM) improved the morphology of DPSC spheroids and increased the expression of odontogenic genes, outperforming the conventional medium, which supports its potential in vital pulp therapy.application/pdfAttribution-NonCommercial-ShareAlike 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-sa/4.0/Acceso abiertohttps://purl.org/coar/access_right/c_abf2http://purl.org/coar/access_right/c_abf2N-AcetilcisteínaCélulas madre mesenquimalesDiferenciación celularTerapia pulpar vitalOdontoblastoN- AcetylcysteineMesenchymal stem cellsCells differentiationVital pulp therapyOdontoblastWU 230Efecto de la N-acetilcisteína sobre la diferenciación a linaje odontoblástico de microesferas de células madre de pulpa dentalEffect of N -acetylcysteine on the differentiation of dental pulp stem cell microspheres into odontoblast lineageEspecialización en endodonciaUniversidad El BosqueFacultad de OdontologíaTesis/Trabajo de grado - Monografía - Especializaciónhttps://purl.org/coar/resource_type/c_7a1fhttp://purl.org/coar/resource_type/c_7a1finfo:eu-repo/semantics/bachelorThesishttps://purl.org/coar/version/c_970fb48d4fbd8a851. K. R. Atkuri, J. J. Mantovani, L. A. Herzenberg, and L. A. Herzenberg, “N-Acetylcysteine–a safe antidote for cysteine/ glutathione deficiency,” Current Opinion in Pharmacology, vol. 7, no. 4, pp. 355–359, 2007.2. Sahasrabudhe SA, Terluk MR, Kartha RV. N-acetylcysteine Pharmacology and Applications in Rare Diseases—Repurposing an Old Antioxidant. Antioxidants [Internet]. 2023 Jun 21;12(7) 1316.3. Pei Y, Liu H, Yang Y, Jiao Y, Tay FR, Chen J. Biological activities and potential oral applications of N-acetylcysteine: progress and prospects. Oxid Med Cell Longev. 2018;2018:2835787. doi:10.1155/2018/2835787.4. Duncan HF. Present status and future directions-Vital pulp treatment and pulp preservation strategies. Int Endod J. 2022 May;55 Suppl 3(Suppl 3):497-511. doi: 10.1111/iej.13688. Epub 2022 Feb 3. PMID: 35080024; PMCID: PMC9306596.5. Duncan HF, Cooper PR., P.R. (2020) Pulp innate immune defense: translational opportunities. Journal of Endodontics, 46, S10–S18.6. Duncan, H.F., Chong, B.S., Del Fabbro, M., El-Karim, I., Galler, K., Kirkevang, L.L. et al. (2021a) The development of European Society of Endodontology S3-level guidelines for the treatment of pulpal and apical disease. International Endodontic Journal, 54, 643–645.7. Asgary, S., Eghbal, M.J., Fazlyab, M., Baghban, A.A. & Ghoddusi, J. (2015) Five-year results of vital pulp therapy in permanent mo-lars with irreversible pulpitis: a non-inferiority multicenter ran-domized clinical trial. Clinical Oral Investigations, 19, 335–341.8. Arora, S., Cooper, P.R., Friedlander, L.T., Rizwan, S., Seo, B., Rich, A.M. et al. (2021) Potential application of immunotherapy for modulation of pulp inflammation: opportunities for vital pulp treatment. International Endodontic Journal, 54, 1263–1274.9. Cui X, Hartanto Y, Zhang H. 2017 Advances in multicellular spheroids formation. J. R. Soc. Interface 14: 20160877. http://dx.doi.org/10.1098/rsif.2016.087710. Y J, Ln N, S M, J L, Fr T, Jh C. Quaternary ammonium-based biomedical materials: State-of-the-art, toxicological aspects and antimicrobial resistance [Internet]. Progress in polymer science. 2017.11. Hahn CL, Liewehr FR. Innate Immune Responses of the Dental Pulp to Caries. Journal of Endodontics. 2007 Jun;33(6):643–51.12. Zheng H, Liu J, Sun L, Meng Z. The role of N-acetylcysteine in osteogenic microenvironment for bone tissue engineering. Front Cell Dev Biol. 2024 Jul 11;12:1435125. doi:10.3389/fcell.2024.1435125. PMID: 39055649; PMCID: PMC11269162.13. Charoenpong H, Osathanon T, Pavasant P, Limjeerajarus N, Keawprachum B, Limjeerajarus CN, et al. Mechanical stress induced S100A7 expression in human dental pulp cells to augment osteoclast differentiation. Oral Diseases. 2019 Jan 25;25(3):812–21.14. Koh AS, Simmons-Willis TA, Pritchard JB, Grassl SM, Ballatori N. Identification of a Mechanism by Which the Methylmercury Antidotes N-Acetylcysteine and Dimercaptopropanesulfonate Enhance Urinary Metal Excretion: Transport by the Renal Organic Anion Transporter-1. Molecular Pharmacology. 2002 oct1;62(4):921–6.15. Bjørndal L, Mjör IA. Pulp-dentin biology in restorative dentistry. Part 4: Dental caries--characteristics of lesions and pulpal reactions. Quintessence International (Berlin, Germany: 1985) [Internet]. 2001 Oct 1;32(9):717–36.16. Yu J, Deng Z, Shi J, Zhai H, Nie X, Zhuang H, et al. Differentiation of Dental Pulp Stem Cells into Regular-Shaped Dentin-Pulp Complex Induced by Tooth Germ Cell Conditioned Medium. Tissue Engineering. 2006 Nov;12(11):3097–105.17. Hybertson BM, Gao B, Bose SK, McCord JM. Oxidative stress in health and disease: the therapeutic potential of Nrf2 activation. Molecular Aspects of Medicine [Internet]. 2011 Aug 1;32(4-6):234–46.18. J. H. Jun, S. H. Lee, H. B. Kwak et al., “N-Acetylcysteine stimulates osteoblastic differentiation of mouse calvarial cells,” Journal of Cellular Biochemistry, vol. 103, no. 4, pp. 1246–1255, 2008.19. F. Pajonk, K. Riess, A. Sommer, and W. H. McBride, “N-Acetyl-L-cysteine inhibits 26S proteasome function: implications for effects on NF-κB activation,” Free Radical Biology & Medicine, vol. 32, no. 6, pp. 536–543, 2002.20. H. Kim, J. Y. Seo, K. H. Roh, J. W. Lim, and K. H. Kim, “Suppression of NF-κB activation and cytokine production by N-acetylcysteine in pancreatic acinar cells,” Free Radical Biology & Medicine, vol. 29, no. 7, pp. 674–683, 2000.21. S. P. Karapinar, Y. Z. A. Ulum, B. Ozcelik et al., “The effect of N-acetylcysteine and calcium hydroxide on TNF-α and TGF- β1 in lipopolysaccharide-activated macrophages,” Archives ofOral Biology, vol. 68, pp. 48–54, 2016.22. D. Y. Kim, J. H. Jun, H. L. Lee et al., “N-Acetylcysteine prevents LPS-induced pro-inflammatory cytokines and MMP2 production in gingival fibroblasts,” Archives of PharmacalResearch, vol. 30, no. 10, pp. 1283–1292, 2007.23. N. Celik, S. Askın, M. A. Gul, and N. Seven, “The effect of restorative materials on cytokines in gingival crevicular fluid,” Archives of Oral Biology, vol. 84, pp. 139–144, 2017.24. Achilli T-M, Meyer J, Morgan JR. 2012 Advances in the formation, use and understanding of multi-cellular spheroids. Expert Opin Biol. Ther. 12, 1347– 1360. (doi:10.1517/14712598.2012.707181)25. J. H. Moon, Y. S. Choi, H. W. Lee, J. S. Heo, S. W. Chang, and J. Y. Lee, “Antibacterial effects of N-acetylcysteine against endodontic pathogens,” Journal of Microbiology, vol. 54, no. 4, pp. 322–329, 2016.26. S. De Flora, A. Izzotti, F. D'Agostini, and R. M. Balansky, “Mechanisms of N-acetylcysteine in the prevention of DNA damage and cancer, with special reference to smokingrelated end-points,” Carcinogenesis, vol. 22, no. 7, pp. 999– 1013, 2001.27. Baker, B.M.,y Chen, C.S. (2012). Deconstructing the third dimension: how 3D culture microenvironments alter cellular cues. J. Cell Sci., 125: 3015-3024.28. Meseguer J, Esteban Abad M de los Á, Mulero Méndez VF, Cuesta Peñafiel A, Sepulcre Cortés MP. Esferoides y esferas líquidas: Cultivos celulares en 3D para mimetizar el ambiente de las células en el organismo. Eubacteria. 2015;(34):2015.29. Choi J, Kim D, Kim M, Kim S, Kim J, Choi Y. Outcomes of direct pulp-capping procedures performed by dental students: A retrospective study. J Am Dent Assoc. 2006;137(12):1699-705.30. Asgary S, Nazarian H, Khojasteh A, Shokouhinejad N. Gene expression and cytokine release during odontogenic differentiation of human dental pulp stem cells induced by 2 endodontic biomaterials. J Endod 2014;40:387-39231. Paranjpe A, Sung EC, Cacalano NA, Hume WR, Jewett A. N-acetylcysteine protects pulp cells from resin toxins in vivo. J Dent Res. 2008;87(6):537–541. doi:10.1177/154405910808700603.32. Diamanti E, Mathieu S, Jeanneau C, et al. Endoplasmic reticulum stress and mineralization inhibition mechanism by the resinous monomer HEMA. Int Endod J 2013;46:160–8.33. Lin RZ, Chang HY. Recent advances in three-dimensional multicellular spheroid culture for biomedical research. Biotechnol J. 2008 Oct;3(9-10):1172-84. doi: 10.1002/biot.200700228. Erratum in: Biotechnol J. 2008 Oct;3(9-10):1285. Lin, Ruei-Zhen [corrected to Lin, Ruei-Zeng]. PMID: 18566957.34. Min KS, Kwon YY, Lee HJ, et al. Effects of proinflammatory cytokines on the expression of mineralization markers and heme oxygenase-1 in human pulp cells. J Endod 2006;32:39–43.35.Takeuchi O, Akira S. Pattern recognition receptors and inflammation. Cell 2010; 140:805–20.36. Margunato S, Tas¸lı PN, Aydın S, et al. In vitro evaluation of ProRoot MTA, Biodentine, and MM-MTA on human alveolar bone marrow stem cells in terms of biocompatibility and mineralization. J Endod 2015;41:1646–52.37. Bortoluzzi EA, Niu LN, Palani CD, et al. Cytotoxicity and osteogenic potential of silicate calcium cements as potential protective materials for pulpal revascularization. Dent Mater 2015;31:1510–22.38. Jang JH, Kang M, Ahn S, et al. Tooth discoloration after the use of new pozzolan cement (Endocem) and mineral trioxide aggregate and the effects of internal bleaching. J Endod 2013;39:1598–60239. Camilleri J., Sorrentino F., Damidot D. Investigation of the hydration and bioactivity of radiopacified tricalcium silicate cement, Biodentine and MTA Angelus. Dental Materials. 2013;29(5):580–593. doi: 10.1016/j.dental.2013.03.007.40. Grech L., Mallia B., Camilleri J. Investigation of the physical properties of tricalcium silicate cement-based root-end filling materials. Dental Materials. 2013;29(2):e20–e28. doi: 10.1016/j.dental.2012.11.007.41. Al-Sherbiny I. M., Farid M. H., Abu-Seida A. M., Motawea I. T., Bastawy H. A. Chemico-physical and mechanical evaluation of three calcium silicate-based pulp capping materials. The Saudi Dental Journal. 2020 doi: 10.1016/j.sdentj.2020.02.00142. Kayahan M. B., Nekoofar M. H., McCann A., et al. Effect of acid etching procedures on the compressive strength of 4 calcium silicate-based endodontic cements. Journal of Endodontia. 2013;39(12):1646–1648. doi: 10.1016/j.joen.2013.09.008.43. Vallés M., Mercadé M., Duran-Sindreu F., Bourdelande J. L., Roig M. Influence of Light and Oxygen on the Color Stability of Five Calcium Silicate- based Materials. Journal of Endodontia. 2013;39(4):525–528. doi: 10.1016/j.joen.2012.12.02144. Palma P. J., Marques J. A., Falacho R. I., et al. Six-month color stability assessment of two calcium silicate-based cements used in regenerative endodontic procedures. Journal of Functional BiomaterialsJournal of Functional Biomaterials. 2019;10(1):p. 14. doi: 10.3390/jfb10010014.45. Duarte M. A. H., Marciano M. A., Vivan R. R., Tanomaru Filho M., Tanomaru J. M. G., Camilleri J. Tricalcium silicate-based cements: properties and modifications. Brazilian Oral Research. 2018;32(Supplement 1):e70–118. doi: 10.1590/1807-3107bor-2018.vol32.007046. Akhlaghi N, Khademi A. Outcomes of vital pulp therapy in permanent teeth with different medicaments: a literature review. Iran Endod J. 2015;10(1):6–14.47. Kearney M, Cooper PR, Smith AJ, Duncan HF. Epigenetic Approaches to the Treatment of Dental Pulp Inflammation and Repair: Opportunities and Obstacles. Front Genet. 2018 Aug 7;9:311. doi: 10.3389/fgene.2018.00311. PMID: 30131827; PMCID: PMC6090030.48. G. F. Rushworth and I. L. Megson, “Existing and potential therapeutic uses for N-acetylcysteine: the need for conversion to intracellular glutathione for antioxidant benefits,” Pharmacology & Therapeutics, vol. 141, no. 2, pp. 150–159, 2014.49. Millea PJ. N-acetylcysteine: multiple clinical applications. Am Fam Physician. 2009 Aug 1;80(3):265-9. PMID: 19621836.50. Shahripour R.B., Harrigan M.R., Alexandrov A.V. N-acetylcysteine (NAC) in neurological disorders: Mechanisms of action and therapeutic opportunities. Brain Behav. 2014;4:108–122. doi: 10.1002/brb3.20851. Schweikl H, Hartmann A, Hiller KA, Spagnuolo G, Bolay C, Brockhoff G, Schmalz G. Inhibition of TEGDMA and HEMA induced genotoxicity and cell cycle arrest by N acetylcysteine. Dent Mater. 2007 Jun;23(6):688–95. doi:10.1016/j.dental.2006.06.02152. Pawar M, Pawar V, Thete SG, et al. Enhance-ment of Odontoblastic Differentiation of Stem Cells from Exfoliated Deciduous Tooth Using N-acetylcysteine—An In Vitro Study. J Contemp Dent Pract 2021;22(8):882–889.53. Piccinini F, Tesei A, Arienti C, Bevilacqua A. AnaSP: a software suite for automatic image analysis of multicellular spheroids. Comput Methods Programs Biomed. 2015;119(1):43–52.54. Zanoni M, Pignatta S, Arienti C, Bonafè M, Tesei A. Anticancer drug discovery using multicellular tumor spheroid models. Expert Opin Drug Discov. 2019;14(3):289–301. doi:10.1080/17460441.2019.1571130.55. Gronthos, S., Mankani, M., Brahim, J., Robey, P. G., & Shi, S. (2000). Postnatal human dental pulp stem cells (DPSCs) in vitro and in vivo. Proceedings of the National Academy of Sciences of the United States of America, 97(25), 13625–13630. https://doi.org/10.1073/pnas.24030979756. Meng Z, Liu J, Feng Z, Guo S, Wang M, Wang Z, et al. N acetylcysteine regulates dental follicle stem cell osteogenesis and alveolar bone repair via ROS scavenging. Stem Cell Res Ther. 2022;13:466.57. Breslin, S., & O'Driscoll, L. (2013). Three-dimensional cell culture: The missing link in drug discovery. Drug Discovery Today, 18(5–6), 240–249. https://doi.org/10.1016/j.drudis.2012.10.00358. Ghoddusi J, Forghani M, Parisai I. New approaches in vital pulp therapy in permanent teeth. Iran Endod J. 2013;8(1):6–15.59. Countryman K, Chen YW, Johnson JD, Paranjpe A. N-acetylcysteine protects the stem cells of the apical papilla. Front Dent Med. 2022;3:848081. doi:10.3389/fdmed.2022.848081spaORIGINALTrabajo de grado.pdfTrabajo de grado.pdfapplication/pdf878815https://pruebas-update-repositorio-unbosque.cloudbiteca.com/bitstreams/7909bd84-d27b-4a01-8a8a-5c4ccca20c5a/downloada26f1bd769f6c595d62a3513d46fb87aMD51trueAnonymousREAD2027-08-09LICENSElicense.txtlicense.txttext/plain; charset=utf-82000https://pruebas-update-repositorio-unbosque.cloudbiteca.com/bitstreams/94ecd05e-d657-466b-b34f-60eb7c0e45ee/download17cc15b951e7cc6b3728a574117320f9MD55falseAnonymousREADCarta de autorizacion.pdfapplication/pdf370659https://pruebas-update-repositorio-unbosque.cloudbiteca.com/bitstreams/67bfd8dd-70fe-47a4-8faa-872928852b17/download22039ed935b72a3a307053c767754997MD57falseBiblioteca - (Publicadores)READAnexo 1 Acta de aprobacion.pdfapplication/pdf310036https://pruebas-update-repositorio-unbosque.cloudbiteca.com/bitstreams/5afdedc5-3d40-44e3-97d8-c676c77e8ad2/download6674171e672270513aa8dd573d280be5MD58falseBiblioteca - (Publicadores)READCC-LICENSElicense_rdflicense_rdfapplication/rdf+xml; charset=utf-81160https://pruebas-update-repositorio-unbosque.cloudbiteca.com/bitstreams/0d57d67a-d473-4731-9e17-5dac00d9d8fa/download5643bfd9bcf29d560eeec56d584edaa9MD56falseAnonymousREADTEXTTrabajo de grado.pdf.txtTrabajo de grado.pdf.txtExtracted texttext/plain84905https://pruebas-update-repositorio-unbosque.cloudbiteca.com/bitstreams/9178a908-68fe-4101-88c4-fb6be986adc2/download1ba7d267e69e8dae0cdb9f0a09345f75MD59falseAnonymousREAD2027-08-10THUMBNAILTrabajo de grado.pdf.jpgTrabajo de grado.pdf.jpgGenerated Thumbnailimage/jpeg2697https://pruebas-update-repositorio-unbosque.cloudbiteca.com/bitstreams/ea4a7cd3-9bb7-4a88-9e24-b3db7cb891bd/downloadd134737a82c561cca33196ccaa3b3acaMD510falseAnonymousREAD2027-08-1020.500.12495/15695oai:pruebas-update-repositorio-unbosque.cloudbiteca.com:20.500.12495/156952025-08-12T10:05:37.746Zhttp://creativecommons.org/licenses/by-nc-sa/4.0/Attribution-NonCommercial-ShareAlike 4.0 Internationalembargo2027-08-09https://pruebas-update-repositorio-unbosque.cloudbiteca.comRepositorio Institucional Universidad El Bosquebibliotecas@biteca.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

Efecto de la N-acetilcisteína sobre la diferenciación a linaje odontoblástico de microesferas de células madre de pulpa dental

Publicaciones similares