IN SITU AND IN SILICO MODELING OF THE HEMATOPOIESIS-INDUCING EFFECT OF CHELIDONIC ACID

AbstractIntroduction. The current trend in regenerative medicine, in the context of an aging population, is the search for new ways and means to optimize tissue bioengineering. One of the convenient models for in situ studying bone marrow regeneration is the subcutaneous ectopic osteogenesis test on scaffolds that imitate the architecture of bone tissue. Chelidonic acid (CA), a small molecule, is capable of participating in various cellular processes and metabolic pathways, and it can activate the osteogenic differentiation of mesenchymal stem cells. However, the molecular mechanisms behind the regulatory effects of CA remain unknown.The purpose of the study. The aim of this study was to investigate the modulatory effect of CA on the in situ formation of hematopoietic foci, as well as to predict target genes and intracellular signaling pathways involved in the hematopoietic activity of CA.Materials and methods. An aqueous solution of CA, isolated from an extract of the Saussurea controversa plant. Course (daily for 35 days) oral administration of CA. Ectopic osteogenesis testing in Balb/c mice. Morphometric analysis of histological sections after 45 days and in silico modelling of gene expression with statistical analysis.Results. CA, when administered orally in a low dose (10 mg / kg), threefold increases the normalized area of bone marrow in the composition of bone tissue plates grown in situ in a test of ectopic subcutaneous osteogenesis in mice. This effect is associated essentially (a probability of CA activity Pa > 0.5 and a probability of inactivity Pi < 0.5) with enhanced expression of 358 hematopoiesis-related genes, as predicted by in silico analysis. The top list with the highest Pa value included 10 target genes, such as GATA1, CITED2, SFRP1, EP300, LGALS9, VNN1, IL10RB, RARA, CD83, and HMOX1.Conclusion. CA has a significant ability to enhance the reparative remodeling of hematopoietic tissue in situ. The next phase of research will be to test actual target genes and signaling pathways that mediate the regulatory effect of HC on hematopoiesis both in vitro and in vivo, as well as in clinical settings.