Institute of Crystallography - CNR

Biological effects of space environment and development of effective countermeasures

Studies on the bone matrix biomineralization and genetic and epigenetic regulation are performed in model systems and biologic fluids collected from astronauts before, during and after space flights, to develop effective countermeasures for microgravity-induced osteoporosis.

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)

Reference works

– F. Cristofaro, G. Pani, B. Pascucci, A. Mariani, M. Balsamo, A. Donati, G. Mascetti, G. Rea, A.M. Rizzo, L. Visai (2019). The NATO project: nanoparticle-based countermeasures for microgravity-induced Osteoporosis. Scientific Reports, 9:17141.
– Campi G., Cristofaro F., Pani G., Fratini M., Pascucci B., Corsetto P.A., Weinhauseng B., Cedola A., Rizzo A.M., Visai L. and Rea G. (2017). Heterogeneous and self-organizing mineralization of bone matrix promoted by hydroxyapatite nanoparticles. Nanoscale 9(44), 17274-17283.
– G. Rea, F. Cristofaro, G. Pani, B. Pascucci, S.A. Ghuge, P.A. Corsetto, M. Imbriani, L. Visai, A. M. Rizzo (2016) Microgravity-driven remodeling of the proteome reveals insights into molecular mechanisms and signal networks involved in response to the space flight environment. Journal of Proteomics, 137, 3-18.