Gioia Madga

Evaluation of cell response to mechanical stimuli in human primary cells

Gioia Ma, Marini Mb, Rinaldi AMb,  Michaletti Ac, Scimeca Md, Zolla Lc, Tarantino Ua,dand  Coletta Ma
aDepartment of Clinical Medicine and Translational Science and bDepartment of System Medicine, University  of  Rome Tor Vergata, c Department of Ecological and Biological Sciences University of Tuscia, Viterbo , dDepartment of Orthopaedic surgery and Traumatology, Hospital of  Tor Vergata.  

Decreased mechanical loading on bones, such as prolonged bed rest and microgravity during space flights, leads to the development of an osteoporotic-like phenotype. Although osteoblast hypo-functionality is reported to be involved in the progression of bone pathological conditions, the cellular mechanisms of this process remain largely unknown. The combined application of mass spectrometry “–omics” and histochemical and ultrastructural approaches has been employed to investigate the effects of the gravitational unloading (Sμg) on human bonecell biology. The effect of weightless conditions on osteogenesis, comparing cellular morphology, proteome profiling, metabolism and cell motility between hpOBs exposed to Sμg versus those kept under normo-gravity conditions were examided. Overall, this investigation gives a functional and morphological overview of how hpOBs receive an impulse to dedifferentiate by gravitational unloading. We reported that Sμg changes cell metabolism, as revealed by an increased glycolysis pathways and by a severe impairment of the Krebs cycle pathway associated to a decrease of the malate-aspartate shuttle. This was related to a significant alteration of chain electron transport of respiratory proteins, mainly affecting complex IIIThereby suggesting that Sμg suppresses bone cell functions through a prominent dysregulation of mitochondria, which impairs the energy state and antioxidant capacity of hpOB cells. Present findings suggest that simulated Sμg could be employed to promote cell dedifferentiation and potentially be addressed to trans-differentiate to alternative cell types. Clearly, the complexity of dedifferentiation processes deserves further studies to understand more accurately how they work and eventually to harness them for use in regenerative medicine. On the other hand, ex vivo, screening of unloading treatments on hpOBs from osteodegenerative patients could be of help for developing a rational new therapeutically biomechanical strategies for the treatment of skeletal disorders on Earth and to assure safe and effective aerospace missions.