Biological effects of space environment and development of effective countermeasures

Bone remodelling is a fundamental process enabling adaptation of bone architecture to development and repair cues, and maintenance of mineral homeostasis. Impairment in the balance between bone resorption and bone formation contributes to pathologic phenotypes, including among other, osteoporosis. Advances in understanding the molecular and biochemical mechanisms underlying bone remodeling could support the identification of novel targets for drug design and pharmacological interventions. In this framework, space research programmes offer the opportunity to study this active and dynamic process in the presence of microgravity and ionizing radiation, which are well-established determinants reducing bone density and increasing skeletal fragility. In the last decades, the intervention of nanostructured materials for bone regenerative medicine has gained increasing interest. In this context, a multidisciplinary study was conducted on adult mesenchymal cells exposed to real (ISS) and simulated microgravity during differentiation to osteoblasts, treated and not with differentially substituted nano-hydroxyapatites, as a possible countermeasure for microgravity-induced osteoporosis (NATO Project). The biomineralization process was evaluated by high spatial-resolution structural studies (X-ray microdiffraction), and bone metabolism by gene expression of differentiation markers. The upcoming molecular (genetic/epigenetic) analyses on the biological fluids of astronauts will provide indications on biomarkers of exposure as new possible therapeutic targets (Project COMET-ISS)