TY  - JOUR
AU  - Vuković, Mladen
AU  - Lazarević, Miloš
AU  - Mitić, Dijana
AU  - Jakšić Karišik, Milica
AU  - Ilić, Branislav
AU  - Andrić, Miroslav
AU  - Jevtić, Bojan
AU  - Roganović, Jelena
AU  - Milašin, Jelena
PY  - 2022
UR  - http://radar.ibiss.bg.ac.rs/handle/123456789/5164
AB  - OBJECTIVE The study aimed to investigate acetylsalicylic acid (ASA) effects on osteo/odontogenic differentiation and proliferation of dental pulp stem cells (DPSCs) in vitro and the potential involvement of adenosine monophosphate-activated protein kinase (AMPK) pathway in these processes. DESIGN DPSCs were isolated from third molars pulp tissues of five patients and grown in osteogenic medium alone or supplemented with ASA. Expression of DPSCs markers was tested by flow-cytometry. Cytotoxicity of ASA at concentrations of 10, 50 and 100 µg/ml was tested by MTT and NR assays. Osteo/odontogenic differentiation was analyzed via alizarin red staining and ALP activity. Quantitative PCR (qPCR) was used for osteo/odontogenic markers' (DSPP, BMP2, BMP4, BSP, OCN and RUNX2) and c-Myc expression analysis. AMPK inhibition of ASA-induced osteo/odontogenesis was tested by qPCR of selected markers (DSPP, OCN and RUNX2). RESULTS Cytotoxicity assays showed that only the highest ASA dose decreased cell viability (89.1 %). The smallest concentration of ASA applied on DPSCs resulted in a remarkable enhancement of osteo/odontogenic differentiation, as judged by increased mineralized nodules' formation, ALP activity and gene expression of analyzed markers (increase between 2 and 30 folds), compared to untreated cells. ASA also increased DPSCs proliferation. Interestingly, AMPK inhibition per se upregulated DSPP, OCN and RUNX2; the gene upregulation was higher when ASA treatment was also included. c-Myc expression level decreased in cultures treated with ASA, indicating undergoing differentiation processes. CONCLUSIONS Low concentrations of ASA (corresponding to the standard use in cardiovascular patients), were shown to stimulate osteo/odontogenic differentiation of dental pulp stem cells.
PB  - Oxford: Pergamon-Elsevier Science Ltd
T2  - Archives of Oral Biology
T1  - Acetylsalicylic-acid (ASA) regulation of osteo/odontogenic differentiation and proliferation of human dental pulp stem cells (DPSCs) in vitro.
VL  - 144
DO  - 10.1016/j.archoralbio.2022.105564
SP  - 105564
ER  - 

@article{
author = "Vuković, Mladen and Lazarević, Miloš and Mitić, Dijana and Jakšić Karišik, Milica and Ilić, Branislav and Andrić, Miroslav and Jevtić, Bojan and Roganović, Jelena and Milašin, Jelena",
year = "2022",
abstract = "OBJECTIVE The study aimed to investigate acetylsalicylic acid (ASA) effects on osteo/odontogenic differentiation and proliferation of dental pulp stem cells (DPSCs) in vitro and the potential involvement of adenosine monophosphate-activated protein kinase (AMPK) pathway in these processes. DESIGN DPSCs were isolated from third molars pulp tissues of five patients and grown in osteogenic medium alone or supplemented with ASA. Expression of DPSCs markers was tested by flow-cytometry. Cytotoxicity of ASA at concentrations of 10, 50 and 100 µg/ml was tested by MTT and NR assays. Osteo/odontogenic differentiation was analyzed via alizarin red staining and ALP activity. Quantitative PCR (qPCR) was used for osteo/odontogenic markers' (DSPP, BMP2, BMP4, BSP, OCN and RUNX2) and c-Myc expression analysis. AMPK inhibition of ASA-induced osteo/odontogenesis was tested by qPCR of selected markers (DSPP, OCN and RUNX2). RESULTS Cytotoxicity assays showed that only the highest ASA dose decreased cell viability (89.1 %). The smallest concentration of ASA applied on DPSCs resulted in a remarkable enhancement of osteo/odontogenic differentiation, as judged by increased mineralized nodules' formation, ALP activity and gene expression of analyzed markers (increase between 2 and 30 folds), compared to untreated cells. ASA also increased DPSCs proliferation. Interestingly, AMPK inhibition per se upregulated DSPP, OCN and RUNX2; the gene upregulation was higher when ASA treatment was also included. c-Myc expression level decreased in cultures treated with ASA, indicating undergoing differentiation processes. CONCLUSIONS Low concentrations of ASA (corresponding to the standard use in cardiovascular patients), were shown to stimulate osteo/odontogenic differentiation of dental pulp stem cells.",
publisher = "Oxford: Pergamon-Elsevier Science Ltd",
journal = "Archives of Oral Biology",
title = "Acetylsalicylic-acid (ASA) regulation of osteo/odontogenic differentiation and proliferation of human dental pulp stem cells (DPSCs) in vitro.",
volume = "144",
doi = "10.1016/j.archoralbio.2022.105564",
pages = "105564"
}

Vuković, M., Lazarević, M., Mitić, D., Jakšić Karišik, M., Ilić, B., Andrić, M., Jevtić, B., Roganović, J.,& Milašin, J.. (2022). Acetylsalicylic-acid (ASA) regulation of osteo/odontogenic differentiation and proliferation of human dental pulp stem cells (DPSCs) in vitro.. in Archives of Oral Biology
Oxford: Pergamon-Elsevier Science Ltd., 144, 105564.
https://doi.org/10.1016/j.archoralbio.2022.105564

Vuković M, Lazarević M, Mitić D, Jakšić Karišik M, Ilić B, Andrić M, Jevtić B, Roganović J, Milašin J. Acetylsalicylic-acid (ASA) regulation of osteo/odontogenic differentiation and proliferation of human dental pulp stem cells (DPSCs) in vitro.. in Archives of Oral Biology. 2022;144:105564.
doi:10.1016/j.archoralbio.2022.105564 .

Vuković, Mladen, Lazarević, Miloš, Mitić, Dijana, Jakšić Karišik, Milica, Ilić, Branislav, Andrić, Miroslav, Jevtić, Bojan, Roganović, Jelena, Milašin, Jelena, "Acetylsalicylic-acid (ASA) regulation of osteo/odontogenic differentiation and proliferation of human dental pulp stem cells (DPSCs) in vitro." in Archives of Oral Biology, 144 (2022):105564,
https://doi.org/10.1016/j.archoralbio.2022.105564 . .