Food derived bioactive compounds in cellular regeneration and remodelling of bone and muscle tissue in microgravity conditions: use of big data and high efficiency bioinformatic platforms

To date, there is evidence that altered gravity exerts a modulating effect on cellular gene expression. Such changes may be accompanied by a variation in biomarkers, including microRNAs (miRNAs) released into the bloodstream, that correlate with physiological adaptations and responses to the microgravity environment. This work focused on the role of miRNAs in gene regulation and biological pathways associated with diseases such as muscular atrophy and osteoporosis. Understanding their expression dynamics, identifying target genes and the pathways involved is crucial to assessing their potential for prevention and diagnosis. In addition, food-derived bioactive compounds (BC) can directly or indirectly modulate the expression of miRNAs and associated genes, thereby influencing pathways of cell regeneration and differentiation in bone and muscle tissue. In line with recent scientific findings, our project used an integrated bioinformatics approach to: i) identify the differentially expressed and deregulated miRNAs in osteoporosis, muscle atrophy and microgravity conditions; ii) identify the target genes of these miRNAs and the pathways involved using the MIENTURNET and Reactome tools; iii) explore bioactive compounds capable of modulating identified miRNAs, genes and pathways. The analysis identify a restricted pool of miRNAs shared among the three conditions, significant overlap between genes and pathways common to two or more conditions, suggesting the existence of conserved molecular mechanisms linking bone and muscle degeneration to microgravity-induced changes. Significant interactions were also identified between BC and miRNAs, such as ursolic acid and miR-let-7g-5p or quercetin and miR-206 that highlight an interplay between miRNAs, bioactive compounds, and molecular pathways (such as Regulation of MITF-M-dependent genes involved in apoptosis) in the regeneration of bone tissue. Other BC such as tocotrienol and epicatechin could lead to up-regulation of miR-206 positively influencing myoblast differentiation. Other compounds found through the STITCH database, such as curcumin and carotene, quercetin and myricetin, affect target genes involved in metabolism and tissue remodelling (ccnd1, scarb1, pim1), suggesting that these BC may be able to modulate not only the genes but also the pathways in which they are involved. These results provide new insights into the molecular mechanisms underlying microgravity-induced musculoskeletal disorders and metabolic changes, and highlight the potential of food-derived bioactive compounds as innovative interventions for the prevention and treatment of these conditions, not only in space but also on Earth.