Preview

Bulletin of Siberian Medicine

Advanced search

Osteogenic potential of mesenchymal stem cells of epicardial adipose tissue in patients with coronary heart disease

https://doi.org/10.20538/1682-0363-2025-1-86-95

Abstract

Aim. To assess the osteogenic potential of mesenchymal stem cells (MSCs) of epicardial adipose tissue (EAT) in patients with stable coronary heart disease based on obtaining gene profiles (osteogenesis markers).
Materials and methods. In EAT MSCs, the expression levels of the RUNX2 (RUNX transcription factor encoding gene), BGLAP (osteocalcin encoding gene), SPP1 (osteopontin encoding gene), SP7 (Osterix encoding gene) genes were determined using real-time polymerase chain reaction (PCR). Using immunofluorescence staining, the amount of RUNX2, osteocalcin, osteopontin, and Osterix proteins was determined in the supernatant of cultured MSCs.
Results. It was found that the expression of RUNX2 in cells cultured in a medium with osteoinducers was 1.88 times higher than in undifferentiated MSCs (p = 0.012). The level of RUNX2 protein was also higher in a differentiated cell culture (p < 0.05). Similar results were obtained regarding the level of SPP1 mRNA expression (p = 0.012). BGLAP expression did not differ between differentiated and undifferentiated MSC cultures. The level of SP7 gene expression did not differ in cells either with or without an osteoblastic medium. It is worth noting that using immunofluorescence staining, there were no differences detected in the expression of Osterix and OCN between cultures of differentiated and undifferentiated cells.
Conclusion. It was found that EAT MSCs have osteogenic potential, which was manifested by the expression of osteogenesis genes in both differentiated and undifferentiated MSCs. The increase in the expression level of SSP1 and RUNX2 mRNA on the 15th day of cultivation with osteoblastic medium indicates that the studied cells are preosteoblasts and are at the stage of extracellular matrix synthesis.

About the Authors

E. G. Uchasova
Research Institute for Complex Issues of Cardiovascular Diseases Federal State Budgetary Institution
Russian Federation

6, Blvd. named after academician L.S. Barbarasha, Kemerovo, 650000


Competing Interests:

The authors declare the absence of obvious or potential conflicts of interest related to the publication of this article.



Yu. A. Dyleva
Research Institute for Complex Issues of Cardiovascular Diseases Federal State Budgetary Institution
Russian Federation

6, Blvd. named after academician L.S. Barbarasha, Kemerovo, 650000


Competing Interests:

The authors declare the absence of obvious or potential conflicts of interest related to the publication of this article.



T. A. Slesareva
Research Institute for Complex Issues of Cardiovascular Diseases Federal State Budgetary Institution; Kemerovo State Medical University
Russian Federation

6, Blvd. named after academician L.S. Barbarasha, Kemerovo, 650000;
22a, Voroshilov Str., Kemerovo, 650000


Competing Interests:

The authors declare the absence of obvious or potential conflicts of interest related to the publication of this article.



E. V. Belik
Research Institute for Complex Issues of Cardiovascular Diseases Federal State Budgetary Institution
Russian Federation

6, Blvd. named after academician L.S. Barbarasha, Kemerovo, 650000


Competing Interests:

The authors declare the absence of obvious or potential conflicts of interest related to the publication of this article.



A. V. Ponasenko
Research Institute for Complex Issues of Cardiovascular Diseases Federal State Budgetary Institution
Russian Federation

6, Blvd. named after academician L.S. Barbarasha, Kemerovo, 650000


Competing Interests:

The authors declare the absence of obvious or potential conflicts of interest related to the publication of this article.



E. A. Velikanova
Research Institute for Complex Issues of Cardiovascular Diseases Federal State Budgetary Institution
Russian Federation

6, Blvd. named after academician L.S. Barbarasha, Kemerovo, 650000


Competing Interests:

The authors declare the absence of obvious or potential conflicts of interest related to the publication of this article.



V. G. Matveeva
Research Institute for Complex Issues of Cardiovascular Diseases Federal State Budgetary Institution
Russian Federation

6, Blvd. named after academician L.S. Barbarasha, Kemerovo, 650000


Competing Interests:

The authors declare the absence of obvious or potential conflicts of interest related to the publication of this article.



I. V. Dvadtsatov
Research Institute for Complex Issues of Cardiovascular Diseases Federal State Budgetary Institution
Russian Federation

6, Blvd. named after academician L.S. Barbarasha, Kemerovo, 650000


Competing Interests:

The authors declare the absence of obvious or potential conflicts of interest related to the publication of this article.



O. L. Tarasova
Kemerovo State Medical University
Russian Federation

22a, Voroshilov Str., Kemerovo, 650000


Competing Interests:

The authors declare the absence of obvious or potential conflicts of interest related to the publication of this article.



O. V. Gruzdeva
Research Institute for Complex Issues of Cardiovascular Diseases Federal State Budgetary Institution; Kemerovo State Medical University
Russian Federation

6, Blvd. named after academician L.S. Barbarasha, Kemerovo, 650000;
22a, Voroshilov Str., Kemerovo, 650000


Competing Interests:

The authors declare the absence of obvious or potential conflicts of interest related to the publication of this article.



References

1. Майоров Г.Б., Курбанов С.К., Власова Э.Е., Галяутдинов Д.М., Васильев В.П., Ширяев А.А. и др. Проблема кальциноза при коронарной болезни сердца: вопросы диагностики, прогноза и выбора лечения. Кардиологический вестник. 2018;13(4):4–10. DOI: 10.17116/Cardiobulletin2018130414.

2. Костина Д.А., Успенский В.Е., Семенова Д.С. Mолекулярные механизмы сосудистой кальцификации. Трансляционная медицина. 2020;7(1):6–21. DOI: 10.18705/2311-4495-2020-7-1-6-21.

3. Xie C., Ouyang L., Chen J., Zhang H., Luo P., Wang J. et al. The emerging role of mesenchymal stem cells in vascular calcification. Stem Cells International. 2019:2875189. DOI: 10.1155/2019/2875189.

4. Leszczynska A., Murphy J.M. Vascular calcification: Is it rather a stem/progenitor cells driven phenomenon? Front. Bioeng. Biotechnol. 2018;6:10. DOI: 10.3389/fbioe.2018.00010.

5. Krawczenko A., Klimczak A. Adipose tissue-derived mesenchymal stem/stromal cells and their contribution to angiogenic processes in tissue regeneration. International Journal of Molecular Sciences. 2022;23(5):2425. DOI: 10.3390/ijms23052425.

6. Нимирицкий П., Сагарадзе Г.Д., Ефименко А.Ю. Ниша стволовой клетки. Цитология. 2018;60(8):575–586. DOI: 10.31116/tsitol.2018.08.01.

7. Ozkaynak B., Şahin I., Ozenc E., Subasi C., Oran D.S., Totoz T. et al. Mesenchymal stem cells derived from epicardial adipose tissue reverse cardiac remodeling in a rabbit model of myocardial infarction. European Review for Medical and Pharmacological Sciences. 2021;25(12):4372–4384. DOI: 10.26355/eurrev_202106_26147.

8. Lambert C., Arderiu G., Bejar M.T. et al. Stem cells from human cardiac adipose tissue depots show different gene expression and functional capacities. Stem Cell Research & Therapy. 2019;10(1):361. DOI: 10.1186/s13287-019-1460-1.

9. Malashicheva A., Irtyuga O., Kostina A., Ignatieva E., Zhiduleva E., Semenova D. et al. Osteogenic potential of adipose mesenchymal stem cells is not correlated with aortic valve calcification. Biological Communications. 2018;63(2):117–122.

10. Kostina A., Lobov A., Semenova D., Kiselev A., Klausen P., Malashicheva A. Context-specific osteogenic potential of mesenchymal stem cells. Biomedicines. 2021;9(6):673. DOI: 10.3390/biomedicines9060673.

11. Bourin P., Bunnell B. A., Casteilla L., Dominici M. et al. Stromal cells from the adipose tissue-derived stromal vascular fraction and culture expanded adipose tissue-derived stromal/stem cells: a joint statement of the International Federation for Adipose Therapeutics and Science (IFATS) and the international So. Cytotherapy. 2013;15(6):641–648. DOI: 0.1016/j.jcyt.2013.02.006.

12. Fadini G.P., Rattazzi M., Matsumoto T., Asahara T., Khosla S. Emerging role of circulating calcifying cells in the bone-vascular axis. Circulation. 2012;125(22):2772–2781. DOI: 10.1161/CIRCULATIONAHA.112.090860.

13. Соловьев В.А., Шинкаренко Т.В. Происхождение, дифференцировка и морфофункциональная характеристика клеток костной ткани. Верхневолжский медицинский журнал. 2011;9(3):49–54.

14. Zhou P., Shi J.M., Song J.E., Han Y., Li H.J., Song Y.M. et al. Establishing a deeper understanding of the osteogenic differentiation of monolayer cultured human pluripotent stem cells using novel and detailed analyses. Stem Cell Res. Ther. 2021;12(1):41. DOI: 10.1186/s13287-020-02085-9.

15. Xu J., Li Z., Hou Y., Fang W. Potential mechanisms underlying the Runx2 induced osteogenesis of bone marrow mesenchymal stem cells. American Journal of Translational Research. 2015;7(12):252–235.

16. Komori T. Regulation of proliferation, differentiation and functions of osteoblasts by runx2. International Journal of Molecular Sciences. 2019;20(7):1694. DOI: 10.3390/ijms20071694.

17. Zhou P., Shi J.M., Song J.E. Establishing a deeper understanding of the osteogenic differentiation of monolayer cultured human pluripotent stem cells using novel and detailed analyses. Stem Cell Research & Therapy. 2021;21(12):41. DOI: 10.1186/s13287-020-02085-9.

18. Rashid H., Ma C., Chen H., Wang H., Hassan M.Q. et al. Sp7 and Runx2 molecular complex synergistically regulate expression of target genes. Connect Tissue Research. 2014;55(1):83–87. DOI: 10.3109/03008207.2014.923872.

19. Kawane T., Komori H., Liu W., Moriishi T., Miyazaki T., Mori M. et al. Dlx5 and mef2 regulate a novel runx2 enhancer for osteoblast-specific expression. Journal of Bone and Mineral Research. 2014:29(9):1960–1969. DOI: 10.1002/jbmr.2240.

20. Sinha K.M., Zhou X. Genetic and molecular control of osterix in skeletal formation. Journal of Cellular Biochemistry. 2013;114(5):975–984. DOI: 10.1002/jcb.24439.

21. Pokrovskaya L.A., Nadezhdin S.V., Zubareva E.V., Burda Y.E., Gnezdyukova E.S. Expression of RUNX2 and osterix in rat mesenchymal stem cells during culturing in osteogenic-conditioned medium. Bulletin of Experimental Biology and Medicine. 2020;169(4):571–575. DOI: 10.1007/s10517-020-04931-5.

22. Si J., Wang C., Zhang D., Wang B., Zhou Y. Osteopontin in bone metabolism and bone diseases. Medical Science Monitor. 2020;26:e919159. DOI: 10.12659/MSM.919159.

23. Zoch M.L., Clemens T.L., Riddle R.C. New insights into the biology of osteocalcin. Bone. 2016;82:42–49. DOI: 10.1016/j.bone.2015.05.046.


Review

For citations:


Uchasova E.G., Dyleva Yu.A., Slesareva T.A., Belik E.V., Ponasenko A.V., Velikanova E.A., Matveeva V.G., Dvadtsatov I.V., Tarasova O.L., Gruzdeva O.V. Osteogenic potential of mesenchymal stem cells of epicardial adipose tissue in patients with coronary heart disease. Bulletin of Siberian Medicine. 2025;24(1):86-95. https://doi.org/10.20538/1682-0363-2025-1-86-95

Views: 199


Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.


ISSN 1682-0363 (Print)
ISSN 1819-3684 (Online)