Journal Article

FZJ-2021-03563

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Aza-Reversine Promotes Reprogramming of Lung (MRC-5) and Differentiation of Mesenchymal Cells into Osteoblasts

Tsitouroudi, F. ; Sarli, V. ; Poulcharidis, D. ; Pitou, M. ; Katranidis, A.FZJ* ; Choli-Papadopoulou, T. (Corresponding author)

2021
MDPI Basel

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Please use a persistent id in citations: http://hdl.handle.net/2128/28675  doi:10.3390/ma14185385

Abstract: Reversine or 2-(4-morpholinoanilino)-N6-cyclohexyladenine was originally identified as a small organic molecule that induces dedifferentiation of lineage-committed mouse myoblasts, C2C12, and redirects them into lipocytes or osteoblasts under lineage-specific conditions (LISCs). Further, it was proven that this small molecule can induce cell cycle arrest and apoptosis and thus selectively lead cancer cells to cell death. Further studies demonstrated that reversine, and more specifically the C2 position of the purine ring, can tolerate a wide range of substitutions without activity loss. In this study, a piperazine analog of reversine, also known as aza-reversine, and a biotinylated derivative of aza-reversine were synthesized, and their potential medical applications were investigated by transforming the endoderm originates fetal lung cells (MRC-5) into the mesoderm originated osteoblasts and by differentiating mesenchymal cells into osteoblasts. Moreover, the reprogramming capacity of aza-reversine and biotinylated aza-reversine was investigated against MRC-5 cells and mesenchymal cells after the immobilization on PMMA/HEMA polymeric surfaces. The results showed that both aza-reversine and the biofunctionalized, biotinylated analog induced the reprogramming of MRC-5 cells to a more primitive, pluripotent state and can further transform them into osteoblasts under osteogenic culture conditions. These molecules also induced the differentiation of dental and adipose mesenchymal cells to osteoblasts. Thus, the possibility to load a small molecule with useful “information” for delivering that into specific cell targets opens new therapeutic personalized applications.

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Contributing Institute(s):

1. Zelluläre Strukturbiologie (IBI-6)

Research Program(s):

1. 5241 - Molecular Information Processing in Cellular Systems (POF4-524) (POF4-524)
2. 5352 - Understanding the Functionality of Soft Matter and Biomolecular Systems (POF4-535) (POF4-535)

Appears in the scientific report 2021

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