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 have been employed to investigate the effects of the gravitational unloading on human bone-cell biology. Here we show, ex vivo, that simulated microgravity (Sμg) on human primary osteoblasts (hpOB) induces an alteration of pro-osteogenic determinants (i.e., cell morphology and deposit of hydroxyapatite crystals), accompanied by a downregulation of adhesive proteins and bone differentiation markers (e.g., integrin beta-1, protein folding Crystallin Alpha B (CRYα-B), runt-related transcription factor 2 (RUNX-2), bone morphogenic protein-2 (BMP-2), and receptor activator of nuclear factor kappa-B ligand (RANK-L)), indicating an impairment of osteogenesis. Further, we observed for the first time that Sμg can trigger a transition toward a mesenchymal-like phenotype, in which a mature osteoblast displays an hampered vitamin A metabolism, loses adhesive molecules, gains mesenchymal components (e.g., pre-osteoblast state marker CD44), morphological protrusions (filopodium-like), enhances GTPase activities, which in turn allows it to acquire migrating properties. Although this phenotypic conversion is not complete and can be reversible, Sμg environment proves a plasticity potential hidden on Earth. Overall, our results suggest that Sμg can be a powerful physical cue for triggering ex vivo a dedifferentiation impulse on hpOBs, opening a new scenario of possible innovative therapeutical biomechanical strategies for the treatment of osteo-degenerative diseases.

Gioia, M., Michaletti, A., Scimeca, M., Marini, M., Tarantino, U., Zolla, L., et al. (2018). Simulated microgravity induces a cellular regression of the mature phenotype in human primary osteoblasts. CELL DEATH DISCOVERY, 4(1), 59 [10.1038/s41420-018-0055-4].

Simulated microgravity induces a cellular regression of the mature phenotype in human primary osteoblasts

Gioia, Magda;Scimeca, Manuel;Marini, Mario;Tarantino, Umberto;Coletta, Massimo
2018-01-01

Abstract

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 have been employed to investigate the effects of the gravitational unloading on human bone-cell biology. Here we show, ex vivo, that simulated microgravity (Sμg) on human primary osteoblasts (hpOB) induces an alteration of pro-osteogenic determinants (i.e., cell morphology and deposit of hydroxyapatite crystals), accompanied by a downregulation of adhesive proteins and bone differentiation markers (e.g., integrin beta-1, protein folding Crystallin Alpha B (CRYα-B), runt-related transcription factor 2 (RUNX-2), bone morphogenic protein-2 (BMP-2), and receptor activator of nuclear factor kappa-B ligand (RANK-L)), indicating an impairment of osteogenesis. Further, we observed for the first time that Sμg can trigger a transition toward a mesenchymal-like phenotype, in which a mature osteoblast displays an hampered vitamin A metabolism, loses adhesive molecules, gains mesenchymal components (e.g., pre-osteoblast state marker CD44), morphological protrusions (filopodium-like), enhances GTPase activities, which in turn allows it to acquire migrating properties. Although this phenotypic conversion is not complete and can be reversible, Sμg environment proves a plasticity potential hidden on Earth. Overall, our results suggest that Sμg can be a powerful physical cue for triggering ex vivo a dedifferentiation impulse on hpOBs, opening a new scenario of possible innovative therapeutical biomechanical strategies for the treatment of osteo-degenerative diseases.
2018
Pubblicato
Rilevanza internazionale
Articolo
Sì, ma tipo non specificato
Settore MED/33 - MALATTIE APPARATO LOCOMOTORE
English
Gioia, M., Michaletti, A., Scimeca, M., Marini, M., Tarantino, U., Zolla, L., et al. (2018). Simulated microgravity induces a cellular regression of the mature phenotype in human primary osteoblasts. CELL DEATH DISCOVERY, 4(1), 59 [10.1038/s41420-018-0055-4].
Gioia, M; Michaletti, A; Scimeca, M; Marini, M; Tarantino, U; Zolla, L; Coletta, M
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/203054
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