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Open AccessArticle

Changes in Human Foetal Osteoblasts Exposed to the Random Positioning Machine and Bone Construct Tissue Engineering

Osteoimmunology and Integrative Physiology Laboratory, Department of Biology, Texas Southern University, Cleburne, Houston, TX 77004, USA
Department for Biomedicine, Aarhus University, Wilhelm Meyers Allé 4, DK-8000 Aarhus C, Denmark
Clinic for Plastic, Aesthetic and Hand Surgery, Otto von Guericke University Magdeburg, Leipziger Str. 44, 39120 Magdeburg, Germany
Department of Ophthalmology, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, DK-8200 Aarhus N, Denmark
Max Planck Institute of Biochemistry, Martinsried, Am Klopferspitz 18, 82152 Planegg, Germany
Clinical Oral Research Laboratory, Institute of Clinical Dentistry, UiO, University of Oslo, Geitmyrsveien 71 0455 Oslo, Norway
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2019, 20(6), 1357;
Received: 14 February 2019 / Revised: 4 March 2019 / Accepted: 13 March 2019 / Published: 18 March 2019
(This article belongs to the Special Issue Adaptation of Living Organisms in Space: From Mammals to Plants)
Human cells, when exposed to both real and simulated microgravity (s-µg), form 3D tissue constructs mirroring in vivo architectures (e.g., cartilage, intima constructs, cancer spheroids and others). In this study, we exposed human foetal osteoblast (hFOB 1.19) cells to a Random Positioning Machine (RPM) for 7 days and 14 days, with the purpose of investigating the effects of s-µg on biological processes and to engineer 3D bone constructs. RPM exposure of the hFOB 1.19 cells induces alterations in the cytoskeleton, cell adhesion, extra cellular matrix (ECM) and the 3D multicellular spheroid (MCS) formation. In addition, after 7 days, it influences the morphological appearance of these cells, as it forces adherent cells to detach from the surface and assemble into 3D structures. The RPM-exposed hFOB 1.19 cells exhibited a differential gene expression of the following genes: transforming growth factor beta 1 (TGFB1, bone morphogenic protein 2 (BMP2), SRY-Box 9 (SOX9), actin beta (ACTB), beta tubulin (TUBB), vimentin (VIM), laminin subunit alpha 1 (LAMA1), collagen type 1 alpha 1 (COL1A1), phosphoprotein 1 (SPP1) and fibronectin 1 (FN1). RPM exposure also induced a significantly altered release of the cytokines and bone biomarkers sclerostin (SOST), osteocalcin (OC), osteoprotegerin (OPG), osteopontin (OPN), interleukin 1 beta (IL-1β) and tumour necrosis factor 1 alpha (TNF-1α). After the two-week RPM exposure, the spheroids presented a bone-specific morphology. In conclusion, culturing cells in s-µg under gravitational unloading represents a novel technology for tissue-engineering of bone constructs and it can be used for investigating the mechanisms behind spaceflight-related bone loss as well as bone diseases such as osteonecrosis or bone injuries. View Full-Text
Keywords: osteoblasts; bone; tissue engineering; simulated microgravity; biomarker; cytoskeleton osteoblasts; bone; tissue engineering; simulated microgravity; biomarker; cytoskeleton
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Mann, V.; Grimm, D.; Corydon, T.J.; Krüger, M.; Wehland, M.; Riwaldt, S.; Sahana, J.; Kopp, S.; Bauer, J.; Reseland, J.E.; Infanger, M.; Mari Lian, A.; Okoro, E.; Sundaresan, A. Changes in Human Foetal Osteoblasts Exposed to the Random Positioning Machine and Bone Construct Tissue Engineering. Int. J. Mol. Sci. 2019, 20, 1357.

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