Acetylsalicylic-acid (ASA) regulation of osteo/odontogenic differentiation and proliferation of human dental pulp stem cells (DPSCs) in vitro.
2022
Аутори:
Vuković, MladenLazarević, Miloš
Mitić, Dijana
Jakšić Karišik, Milica
Ilić, Branislav
Andrić, Miroslav
Jevtić, Bojan
Roganović, Jelena
Milašin, Jelena
Тип документа:
Чланак у часопису (Објављена верзија)
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© 2022 Elsevier Ltd.
Метаподаци
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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.
Кључне речи:
Acetylsalicylic acid; Adenosine monophosphate-activated protein kinase (; Dental pulp stem cells; Osteogenic/odontogenic differentiation; ProliferationИзвор:
Archives of Oral Biology, 2022, 144, 105564-Финансирање / пројекти:
- Министарство науке, технолошког развоја и иновација Републике Србије, институционално финансирање - 200129 (Универзитет у Београду, Стоматолошки факултет) (RS-MESTD-inst-2020-200129)
DOI: 10.1016/j.archoralbio.2022.105564
ISSN: 0003-9969
PubMed: 36215814