title: Impact of simulated microgravity on human bone stem cells: New hints for space medicine.
abstract: Bone loss is a well known early event in astronauts and represents one of the major obstacle to space exploration. While an imbalance between osteoblast and osteoclast activity has been described, less is known about the behavior of bone mesenchymal stem cells in microgravity. We simulated microgravity using the Random Positioning Machine and found that mesenchymal stem cells respond to gravitational unloading by upregulating HSP60, HSP70, cyclooxygenase 2 and superoxyde dismutase 2. Such an adaptive response might be involved in inducing the overexpression of some osteogenic transcripts, even though the threshold to induce the formation of bone crystal is not achieved. Indeed, only the addition of an osteogenic cocktail activates the full differentiation process both in simulated microgravity and under static 1G-conditions. We conclude that simulated microgravity alone reprograms bone mesenchymal stem cells towards an osteogenic phenotype which results in complete differentiation only after exposure to a specific stimulus.
authors.affiliation: Dipartimento di Scienze Biomediche e Cliniche L. Sacco, Università di Milano, Milano I-20157, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Cazzaniga
authors.affiliation: Dipartimento di Scienze Biomediche e Cliniche L. Sacco, Università di Milano, Milano I-20157, Italy.
authors.forename: Jeanette A M
authors.initials: JAM
authors.lastname: Maier
authors.affiliation: Dipartimento di Scienze Biomediche e Cliniche L. Sacco, Università di Milano, Milano I-20157, Italy. Electronic address: sara.castiglioni@unimi.it.
authors.forename: Sara
authors.initials: S
authors.lastname: Castiglioni
mesh_terms: D000337:Aerospace Medicine; D001842:Bone and Bones / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D018834:Chaperonin 60 / Q000378:metabolism; D003470:Culture Media / Q000737:chemistry; D051546:Cyclooxygenase 2 / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D024101:Mitochondrial Proteins / Q000378:metabolism; D010012:Osteogenesis; D060888:Real-Time Polymerase Chain Reaction; D013312:Stress, Physiological; D013482:Superoxide Dismutase / Q000378:metabolism; D014893:Weightlessness; D018474:Weightlessness Simulation; D000099156:Superoxide Dismutase 2
chemical_list: D018834:Chaperonin 60; D003470:Culture Media; D051546:Cyclooxygenase 2; D018840:HSP70 Heat-Shock Proteins; D024101:Mitochondrial Proteins; D013482:Superoxide Dismutase; D000099156:Superoxide Dismutase 2; C060293:HSPD1 protein, human; C496540:PTGS2 protein, human
keywords: Microgravity; Osteogenesis; Stem cells; Stress response