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© 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

Abstract

Biodentine, a tricalcium silicate cement, has emerged as a retrograde root-end filling material to promote periapical lesion (PL) healing after apicoectomy. However, its underlying mechanisms remain unclear. This study tested the hypothesis that Biodentine stimulates the osteogenic differentiation of mesenchymal stromal cells (MSCs) derived from PLs. The Biodentine extract (B-Ex) was prepared by incubating polymerized Biodentine in RPMI medium (0.2 g/mL) for three days at 37 °C. B-Ex, containing both released microparticles and soluble components, was incubated with PL-MSCs cultured in either a basal MSC medium or suboptimal osteogenic medium. Osteogenic differentiation was assessed by Alizarin Red staining and the expression of 20 osteoblastogenesis-related genes. Non-cytotoxic concentrations of B-Ex stimulated the proliferation of PL-MSCs and induced their osteogenic differentiation in a dose-dependent manner, with a significantly enhanced effect in suboptimal osteogenic medium. B-Ex upregulated most early and late osteoblastic genes. However, the differentiation process was prolonged, as indicated by the delayed expression of wingless-type MMTV integration site family member 2 (WNT2), bone gamma-carboxyglutamate protein (BGLAP), bone morphogenic protein-2 (BMP-2), growth hormone receptor (GHR), and FOS-like 2, AP-1 transcription factor subunit (FOSL2), compared with their expression under optimal osteogenic conditions. The stimulatory effect of B-Ex was primarily calcium dependent, as it was reduced by 85% when B-Ex was treated with the calcium-chelating agent EGTA. In conclusion, Biodentine promotes the osteogenic differentiation of PL-MSCs in a calcium-dependent manner, supporting its stimulatory role in periapical healing.

Details

Title
Biodentine Stimulates Calcium-Dependent Osteogenic Differentiation of Mesenchymal Stromal Cells from Periapical Lesions
Author
Eraković Mile 1 ; Bekić Marina 2 ; Đokić Jelena 3 ; Tomić Sergej 2 ; Vučević Dragana 4 ; Pavlović Luka 2   VIAFID ORCID Logo  ; Duka Miloš 1 ; Marković Milan 2 ; Bokonjić Dejan 5   VIAFID ORCID Logo  ; Čolić Miodrag 6 

 Clinic for Stomatology, Medical Faculty of the Military Medical Academy, University of Defense, 11154 Belgrade, Serbia; [email protected] (M.E.); [email protected] (M.D.) 
 Institute for the Application of Nuclear Energy, University of Belgrade, 11080 Belgrade, Serbia; [email protected] (M.B.); [email protected] (S.T.); [email protected] (L.P.); [email protected] (M.M.) 
 Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, 11042 Belgrade, Serbia; [email protected] 
 Center for Medical Scientific Information, Faculty of Medicine of the Military Medical Academy, University of Defence, 11040 Belgrade, Serbia; [email protected] 
 Medical Faculty Foča, University of East Sarajevo, 73300 Foča, Bosnia and Herzegovina; [email protected] 
 Medical Faculty Foča, University of East Sarajevo, 73300 Foča, Bosnia and Herzegovina; [email protected], Serbian Academy of Sciences and Arts, 11000 Belgrade, Serbia 
First page
4220
Publication year
2025
Publication date
2025
Publisher
MDPI AG
ISSN
16616596
e-ISSN
14220067
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
3203203762
Copyright
© 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.