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Research Article
Biological mechanisms underlying the inflammatory radicular cyst formation-focus on epithelial proliferation: a systematic review of experimental cell and tissue models
Néstor Ríos-Osorio, Sandra Briñez-Rodríguez, David Betancur-Calle, Marggie Grajales, Óscar Mauricio Jiménez-Peña, Mario Guerrero-Torres, Rafael Fernández-Grisales
Restor Dent Endod 2026;51(1):e7.   Published online February 12, 2026
DOI: https://doi.org/10.5395/rde.2026.51.e7
AbstractAbstract PDFPubReaderePub
Objectives
This study aimed to assess the molecular and cellular mechanisms involved in the epithelial proliferation that leads to the transformation of periapical granulomas (PGs) into inflammatory radicular cysts (IRCs).
Methods
A comprehensive search was conducted in three databases. Experimental, observational, or descriptive studies using human or animal tissue samples, or epithelial cell cultures that assessed the molecular and/or cellular mechanisms driving the proliferation of epithelial rests of Malassez and their role in the transformation of PGs into IRCs were included. The risk of bias and applicability of the included studies were assessed using the QUADAS-2.
Results
Fourteen studies (including 399 samples) met the inclusion criteria for qualitative synthesis. The studies highlight the role of pro-inflammatory cytokines (IL-1β, IL-6), growth factors (EGF, KGF, TGF-β, and IGF), and signaling pathways (NF-κB, MAPK/ERK, PI3K/AKT, and Smad) in the progression of PG to IRC. Biomarkers of epithelial proliferation, such as Ki-67, PCNA, and CD34, are consistently associated with this process, while MMP-13 emerges as a key regulator of epithelial behavior and matrix remodeling.
Conclusions
IRC development arises from a transition from homeostatic to pathological signaling, in which pro-inflammatory mediator levels inside the periapical chronic inflammation override regulatory checkpoints.
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Case Reports
Endodontic micro-resurgery and guided tissue regeneration of a periapical cyst associated to recurrent root perforation: a case report
Fernando Córdova-Malca, Hernán Coaguila-Llerena, Lucía Garré-Arnillas, Jorge Rayo-Iparraguirre, Gisele Faria
Restor Dent Endod 2022;47(4):e35.   Published online September 3, 2022
DOI: https://doi.org/10.5395/rde.2022.47.e35
AbstractAbstract PDFPubReaderePub

Although the success rates of microsurgery and micro-resurgery are very high, the influence of a recurrent perforation combined with radicular cyst remains unclear. A 21-year-old white female patient had a history of root perforation in a previously treated right maxillary lateral incisor. Analysis using cone-beam computed tomography (CBCT) revealed an extensive and well-defined periapical radiolucency, involving the buccal and palatal bone plate. The perforation was sealed with bioceramic material (Biodentine) in the pre-surgical phase. In the surgical phase, guided tissue regeneration (GTR) was performed by combining xenograft (lyophilized bovine bone) and autologous platelet-rich fibrin applied to the bone defect. The root-end preparation was done using an ultrasonic tip. The retrograde filling was performed using a bioceramic material (Biodentine). Histopathological analysis confirmed a radicular cyst. The patient returned to her referring practitioner to continue the restorative procedures. CBCT analysis after 1-year recall revealed another perforation in the same place as the first intervention, ultimately treated by micro-resurgery using the same protocol with GTR, and a bioceramic material (MTA Angelus). The 2-year recall showed healing and bone neoformation. In conclusion, endodontic micro-resurgery with GTR showed long-term favorable results when a radicular cyst and a recurrent perforation compromised the success.

Citations

Citations to this article as recorded by  
  • Outcome of endodontic micro-resurgery: A systematic review
    Faisal Alnassar, Riyadh Alroomy, Qamar Hashem, Abdullah Alqedairi, Nabeel Almotairy
    Saudi Endodontic Journal.2025; 15(2): 112.     CrossRef
  • Platelet-Rich Plasma and Platelet-Rich Fibrin in Endodontics: A Scoping Review
    Simão Rebimbas Guerreiro, Carlos Miguel Marto, Anabela Paula, Joana Rita de Azevedo Pereira, Eunice Carrilho, Manuel Marques-Ferreira, Siri Vicente Paulo
    International Journal of Molecular Sciences.2025; 26(12): 5479.     CrossRef
  • Non-surgical Approach to a Maxillary Cyst-Like Lesion: Orthograde Endodontic Treatment With Neodymium-Doped Yttrium Aluminum Garnet (Nd:YAG) Decontamination of the Canal System
    Beatrice Spaggiari, Paolo Vescovi, Silvia Pizzi, Roberta Iaria, Ilaria Giovannacci
    Cureus.2025;[Epub]     CrossRef
  • Persistent Periradicular Lesion Associated With Concurrent Root Fracture and Odontogenic Keratocyst: A Case Report
    Mehdi Vatanpour, Fatemeh Rezaei
    Clinical Case Reports.2025;[Epub]     CrossRef
  • Management of Apico-marginal Defects With Endodontic Microsurgery and Guided Tissue Regeneration: A Report of Thirteen Cases
    Abayomi O. Baruwa, Jorge N.R. Martins, Mariana D. Pires, Beatriz Pereira, Pedro May Cruz, António Ginjeira
    Journal of Endodontics.2023; 49(9): 1207.     CrossRef
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  • 4 Web of Science
  • 5 Crossref
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Progression of periapical cystic lesion after incomplete endodontic treatment
Jong-Ki Huh, Dong-Kyu Yang, Kug-Jin Jeon, Su-Jung Shin
Restor Dent Endod 2016;41(2):137-142.   Published online February 22, 2016
DOI: https://doi.org/10.5395/rde.2016.41.2.137
AbstractAbstract PDFPubReaderePub

We report a case of large radicular cyst progression related to endodontic origin to emphasize proper intervention and follow-up for endodontic pathosis. A 25 yr old man presented with an endodontically treated molar with radiolucency. He denied any intervention because of a lack of discomfort. Five years later, the patient returned. The previous periapical lesion had drastically enlarged and involved two adjacent teeth. Cystic lesion removal and apicoectomy were performed on the tooth. Histopathological analysis revealed that the lesion was an inflammatory radicular cyst. The patient did not report any discomfort except for moderate swelling 3 days after the surgical procedure. Although the patient had been asymptomatic, close follow-ups are critical to determine if any periapical lesions persist after root canal treatment.

Citations

Citations to this article as recorded by  
  • Prognosis of Vital Teeth Involved in Large Cystic Lesions After a Surgical Intervention: A Longitudinal Ambidirectional Cohort Study
    Khalid A. Merdad, Maha Shawky, Khalid A. Aljohani, Rawia Alghamdi, Saja Alzahrani, Omar R. Alkhattab, Abdulaziz Bakhsh
    Dentistry Journal.2025; 13(2): 83.     CrossRef
  • Assessing the efficacy of apicoectomy without retrograde filling in treating periapical inflammatory cysts
    Jeong-Kui Ku, Woo-Young Jeon, Seung-O Ko, Ji-Young Yoon
    Journal of the Korean Association of Oral and Maxillofacial Surgeons.2024; 50(3): 140.     CrossRef
  • Cystic lesion between a deciduous tooth and the succeeding permanent tooth: a retrospective analysis of 87 cases
    Changmo Sohn, Jihye Ryu, Inhye Nam, Sang-Hun Shin, Jae-Yeol Lee
    Journal of the Korean Association of Oral and Maxillofacial Surgeons.2022; 48(6): 342.     CrossRef
  • The effectiveness of antibacterial treatment of the root canal in chronic apical periodontitis using an erbium-chromium laser
    M. A. Postnikov, A. Yu. Rozenbaum, S. E. Chigarina, D. N. Kudryashov, M. B. Khaikin, I. V. Khramova, G. N. Belanov
    Endodontics Today.2022; 20(2): 115.     CrossRef
  • Factors Associated with Incomplete Endodontic Care
    Carla Y. Falcon, Anthony R. Arena, Rebecca Hublall, Craig S. Hirschberg, Paul A. Falcon
    Journal of Endodontics.2021; 47(9): 1398.     CrossRef
  • Tratamento cirúrgico e conservador de cisto periapical de grande proporção: relato de caso
    Maraísa Aparecida Pinto Resende, Neuza Maria Souza Picorelli Assis, Augusto César Sette-Dias, Evandro Guimarães de Aguiar, Bruno Salles Sotto-Maior
    HU Revista.2018; 43(2): 191.     CrossRef
  • 2,885 View
  • 15 Download
  • 6 Crossref
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