Abstract
Despite the great progress in the field of bone tissue regeneration, the early initiating mechanisms of osteogenic differentiation are not well understood. Cells capable of osteogenic transformation vary from mesenchymal stem cells of various origins to mural cells of vessels. The mechanisms of pathological calcification are thought to be similar to those of bone formation. Notch signaling has been shown to play an important role in osteogenic differentiation, as well as in pathological calcification. Nevertheless, despite its known tissue- and context-specificity, the information about its role in the osteogenic differentiation of different cells is still limited. We compared mesenchymal stem cells from adipogenic tissue (MSCs) and interstitial cells from the aortic valve (VICs) by their ability to undergo Notch-dependent osteogenic differentiation. We showed differences between the two types of cells in their ability to activate the expression of proosteogenic genes RUNX2, BMP2, BMP4, DLX2, BGLAP, SPRY, IBSP, and SPP1 in response to Notch activation. Untargeted metabolomic profiling also confirms differences between MSCs and VICs in their osteogenic state. Analysis of the activity of RUNX2 and SPP1 promoters shows fine-tuned dose-dependency in response to Notch induction and suggests a direct link between the level of Notch activation, and the proostogenic gene expression and corresponding osteogenic induction. Our data suggest that osteogenic differentiation is a context-dependent process and the outcome of it could be cell-type dependent.
Highlights
Mesenchymal stem cells of various origins (MSCs) have high proliferative and differentiation potentials, but the mechanisms and factors affecting the ability of cells to transform into tissue-specific somatic cells remain largely unclear [1]
Hairy/enhancer-of-split related with YRPW motif protein 1 (HEY1) was analyzed by qPCR after either 4 or 10 days of differentiation (A) and osteogenic differentiation was analyzed by analyzed by qPCR after either 4 or 10 days of differentiation (A) and osteogenic differentiation was analyzed by alizarin alizarin staining staining (B). (B)
The expression of the key proosteogenic marker Runt-Related Transcription Factor 2 (RUNX2) significantly increased in the presence of Notch activation upon the induction of osteogenic differentiation, and decreased in mesenchymal stem cells (MSCs) by day 10 of osteogenic differentiation compared with valve interstitial cells (VICs)
Summary
Mesenchymal stem cells of various origins (MSCs) have high proliferative and differentiation potentials, but the mechanisms and factors affecting the ability of cells to transform into tissue-specific somatic cells remain largely unclear [1]. Controversial data exist regarding the role of Notch activation in promoting or preventing osteogenic differentiation [7,9,10,11,12,13,14,15], but it is well accepted that Notch signaling preventing differentiation but it We is well accepted. MSCs in of Notch promotes the osteogenic differentiation of adipose-tissue derived. We assumed that there are might be differences in the effect of Notch-signaling on the osteogenic differentiation of mesenchymal cells from various tissues. Cells in terms of their ability to undergo Notch-dependent osteogenic differentiation
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
