Abstract
Aim.Calcified aortic valve stenosis is the third leading cause of cardiovascular disease. The mechanisms underlying this process remain unclear, however, it is known that they are largely similar to the formation of bone tissue during embryonic development, as well as in the postnatal period during regeneration. There is evidence for the involvement of Zinc Finger and BTB Domain Containing 16 (ZBTB16) in skeletal development. At the same time, a number of studies carried out on different types of cell cultures indicate a contradictory and ambiguous effect of ZBTB16 on RUNX2 expression. Thus, the aim of this study was to investigate the dynamic variability of ZBTB16 expression, as well as its role in aortic valve calcification.Methods.The study used different types of mesenchymal cells cultures - aortic valve interstitial cells, umbilical cord mesenchymal stem cells, ligament stem cells and dental pulp stem cells. Changes in ZBTB16 and RUNX2 expression levels under the influence of osteogenic stimuli, as well as during exogenous activation of ZBTB16, were analyzed using real-time PCR. Expression levels of some osteogenic markers - BMP2,4, COL1A1, IBSP, DLX2, PDK4 - were analyzed in the interstitial cells of the aortic valve.Results.The results of the study indicate that a significant increase in the expression of ZBTB16 is observed during the induction of osteogenic differentiation of various cell cultures - interstitial cells of the aortic valve, mesenchymal stem cells of the umbilical cord, stem cells of the ligaments and dental pulp. Apparently, the processes of osteogenic differentiation of aortic valve interstitial cells, in the presence of dexamethasone in cultivation medium, are provided through RUNX2-dependent signaling for the further activation of osteogenic markers.Conclusion.The study of modulation of cellular signals by ZBTB16, when activating or suppressing the work of a transcriptional factor, in the future may bring us closer to the ability to enhance the regenerative abilities of bone tissue cells or, conversely, prevent calcification of the aortic valve tissues.
Highlights
Чрезвычайно важная задача регенеративной медицины – нахождение решения эффективного наращивания и восстановления костной ткани, в том числе при помощи остеогенной дифференцировки мезенхимальных стволовых клеток
Modulating cellular signals by either activating or suppressing Zinc Finger and BTB Domain Containing 16 (ZBTB16) transcriptional factor may bring us closer to the ability to enhance the regenerative abilities of bone tissue cells or, prevent calcification of the aortic valve tissues
The results of the study indicate that a significant increase in the expression of ZBTB16 is observed during the induction of osteogenic differentiation of various cell cultures – interstitial cells of the aortic valve, mesenchymal stem cells of the umbilical cord, stem cells of the ligaments and dental pulp
Summary
Чрезвычайно важная задача регенеративной медицины – нахождение решения эффективного наращивания и восстановления костной ткани, в том числе при помощи остеогенной дифференцировки мезенхимальных стволовых клеток. Какие молекулярные компоненты и каким образом они принимают участие на разных стадиях остеодифференцировки, является первым шагом к возможности управлять процессами остеогенеза. Способность модуляции клеточных сигналов, в том числе за счет активации или подавления работы ZBTB16, возможно, приблизит нас к умению усиливать остеогенез либо предотвращать нежелательную остеогенную дифференцировку в местах эктопической оссификации. Это станет уникальным решением для лечения множества заболеваний
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