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 . .

TY  - JOUR
AU  - Živadinović, Milka
AU  - Andrić, Miroslav
AU  - Milošević, Verica
AU  - Manojlović-Stojanoski, Milica
AU  - Prokić, Branislav
AU  - Prokić, Bogomir
AU  - Dimić, Aleksandar
AU  - Ćalasan, Dejan
AU  - Brković, Božidar
PY  - 2016
UR  - http://www.doiserbia.nb.rs/Article.aspx?ID=0042-84501600013Z
UR  - https://radar.ibiss.bg.ac.rs/handle/123456789/2502
AB  - Background/Aim. The mechanism of impaired bone healing in diabetes mellitus includes different tissue and cellular level activities due to micro- and macrovascular changes. As a chronic metabolic disease with vascular complications, diabetes affects a process of bone regeneration as well. The therapeutic approach in bone regeneration is based on the use of osteoinductive autogenous grafts as well as osteoconductive synthetic material, like a β-tricalcium phosphate. The aim of the study was to determine the quality and quantity of new bone formation after the use of autogenous bone and β-tricalcium phosphate in the model of calvarial critical-sized defect in rabbits with induced diabetes mellitus type I. Methods. The study included eight 4-month-old Chincilla rabbits with alloxan-induced diabetes mellitus type I. In all animals, there were surgically created two calvarial bilateral defects (diameter 12 mm), which were grafted with autogenous bone and β-tricalcium phosphate (n = 4) or served as unfilled controls (n = 4). After 4 weeks of healing, animals were sacrificed and calvarial bone blocks were taken for histologic and histomorphometric analysis. Beside descriptive histologic evaluation, the percentage of new bone formation, connective tissue and residual graft were calculated. All parameters were statistically evaluated by Friedman Test and post hock Wilcoxon Singed Ranks Test with a significance of p < 0.05. Results. Histology revealed active new bone formation peripherally with centrally located connective tissue, newly formed woven bone and well incorporated residual grafts in all treated defects. Control samples showed no bone bridging of defects. There was a significantly more new bone in autogeonous graft (53%) compared with β-tricalcium phosphate (30%), (p < 0.030) and control (7%), (p < 0.000) groups. A significant difference was also recorded between β-tricalcium phosphate and control groups (p < 0.008). Conclusion. In the present study on the rabbit grafting model with induced diabetes mellitus type I, the effective bone regeneration of critical bone defects was obtained using autogenous bone graft.
T2  - Vojnosanitetski pregled
T1  - Histomorphometric evaluation of bone regeneration using autogenous bone and beta-tricalcium phosphate in diabetic rabbits
IS  - 12
VL  - 73
DO  - 10.2298/VSP151125013Z
SP  - 1132
EP  - 1138
ER  - 

@article{
author = "Živadinović, Milka and Andrić, Miroslav and Milošević, Verica and Manojlović-Stojanoski, Milica and Prokić, Branislav and Prokić, Bogomir and Dimić, Aleksandar and Ćalasan, Dejan and Brković, Božidar",
year = "2016",
abstract = "Background/Aim. The mechanism of impaired bone healing in diabetes mellitus includes different tissue and cellular level activities due to micro- and macrovascular changes. As a chronic metabolic disease with vascular complications, diabetes affects a process of bone regeneration as well. The therapeutic approach in bone regeneration is based on the use of osteoinductive autogenous grafts as well as osteoconductive synthetic material, like a β-tricalcium phosphate. The aim of the study was to determine the quality and quantity of new bone formation after the use of autogenous bone and β-tricalcium phosphate in the model of calvarial critical-sized defect in rabbits with induced diabetes mellitus type I. Methods. The study included eight 4-month-old Chincilla rabbits with alloxan-induced diabetes mellitus type I. In all animals, there were surgically created two calvarial bilateral defects (diameter 12 mm), which were grafted with autogenous bone and β-tricalcium phosphate (n = 4) or served as unfilled controls (n = 4). After 4 weeks of healing, animals were sacrificed and calvarial bone blocks were taken for histologic and histomorphometric analysis. Beside descriptive histologic evaluation, the percentage of new bone formation, connective tissue and residual graft were calculated. All parameters were statistically evaluated by Friedman Test and post hock Wilcoxon Singed Ranks Test with a significance of p < 0.05. Results. Histology revealed active new bone formation peripherally with centrally located connective tissue, newly formed woven bone and well incorporated residual grafts in all treated defects. Control samples showed no bone bridging of defects. There was a significantly more new bone in autogeonous graft (53%) compared with β-tricalcium phosphate (30%), (p < 0.030) and control (7%), (p < 0.000) groups. A significant difference was also recorded between β-tricalcium phosphate and control groups (p < 0.008). Conclusion. In the present study on the rabbit grafting model with induced diabetes mellitus type I, the effective bone regeneration of critical bone defects was obtained using autogenous bone graft.",
journal = "Vojnosanitetski pregled",
title = "Histomorphometric evaluation of bone regeneration using autogenous bone and beta-tricalcium phosphate in diabetic rabbits",
number = "12",
volume = "73",
doi = "10.2298/VSP151125013Z",
pages = "1132-1138"
}

Živadinović, M., Andrić, M., Milošević, V., Manojlović-Stojanoski, M., Prokić, B., Prokić, B., Dimić, A., Ćalasan, D.,& Brković, B.. (2016). Histomorphometric evaluation of bone regeneration using autogenous bone and beta-tricalcium phosphate in diabetic rabbits. in Vojnosanitetski pregled, 73(12), 1132-1138.
https://doi.org/10.2298/VSP151125013Z

Živadinović M, Andrić M, Milošević V, Manojlović-Stojanoski M, Prokić B, Prokić B, Dimić A, Ćalasan D, Brković B. Histomorphometric evaluation of bone regeneration using autogenous bone and beta-tricalcium phosphate in diabetic rabbits. in Vojnosanitetski pregled. 2016;73(12):1132-1138.
doi:10.2298/VSP151125013Z .

Živadinović, Milka, Andrić, Miroslav, Milošević, Verica, Manojlović-Stojanoski, Milica, Prokić, Branislav, Prokić, Bogomir, Dimić, Aleksandar, Ćalasan, Dejan, Brković, Božidar, "Histomorphometric evaluation of bone regeneration using autogenous bone and beta-tricalcium phosphate in diabetic rabbits" in Vojnosanitetski pregled, 73, no. 12 (2016):1132-1138,
https://doi.org/10.2298/VSP151125013Z . .