{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T23:52:25Z","timestamp":1775087545970,"version":"3.50.1"},"reference-count":90,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2019,3,18]],"date-time":"2019-03-18T00:00:00Z","timestamp":1552867200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Human cells, when exposed to both real and simulated microgravity (s-\u00b5g), 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-\u00b5g 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-1\u03b2) and tumour necrosis factor 1 alpha (TNF-1\u03b1). After the two-week RPM exposure, the spheroids presented a bone-specific morphology. In conclusion, culturing cells in s-\u00b5g 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.<\/jats:p>","DOI":"10.3390\/ijms20061357","type":"journal-article","created":{"date-parts":[[2019,3,18]],"date-time":"2019-03-18T12:18:53Z","timestamp":1552911533000},"page":"1357","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":42,"title":["Changes in Human Foetal Osteoblasts Exposed to the Random Positioning Machine and Bone Construct Tissue Engineering"],"prefix":"10.3390","volume":"20","author":[{"given":"Vivek","family":"Mann","sequence":"first","affiliation":[{"name":"Osteoimmunology and Integrative Physiology Laboratory, Department of Biology, Texas Southern University, Cleburne, Houston, TX 77004, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniela","family":"Grimm","sequence":"additional","affiliation":[{"name":"Department for Biomedicine, Aarhus University, Wilhelm Meyers All\u00e9 4, DK-8000 Aarhus C, Denmark"},{"name":"Clinic for Plastic, Aesthetic and Hand Surgery, Otto von Guericke University Magdeburg, Leipziger Str. 44, 39120 Magdeburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3588-6350","authenticated-orcid":false,"given":"Thomas J","family":"Corydon","sequence":"additional","affiliation":[{"name":"Department for Biomedicine, Aarhus University, Wilhelm Meyers All\u00e9 4, DK-8000 Aarhus C, Denmark"},{"name":"Department of Ophthalmology, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, DK-8200 Aarhus N, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1120-0246","authenticated-orcid":false,"given":"Marcus","family":"Kr\u00fcger","sequence":"additional","affiliation":[{"name":"Clinic for Plastic, Aesthetic and Hand Surgery, Otto von Guericke University Magdeburg, Leipziger Str. 44, 39120 Magdeburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Markus","family":"Wehland","sequence":"additional","affiliation":[{"name":"Clinic for Plastic, Aesthetic and Hand Surgery, Otto von Guericke University Magdeburg, Leipziger Str. 44, 39120 Magdeburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefan","family":"Riwaldt","sequence":"additional","affiliation":[{"name":"Department for Biomedicine, Aarhus University, Wilhelm Meyers All\u00e9 4, DK-8000 Aarhus C, Denmark"},{"name":"Clinic for Plastic, Aesthetic and Hand Surgery, Otto von Guericke University Magdeburg, Leipziger Str. 44, 39120 Magdeburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jayashree","family":"Sahana","sequence":"additional","affiliation":[{"name":"Department for Biomedicine, Aarhus University, Wilhelm Meyers All\u00e9 4, DK-8000 Aarhus C, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sascha","family":"Kopp","sequence":"additional","affiliation":[{"name":"Clinic for Plastic, Aesthetic and Hand Surgery, Otto von Guericke University Magdeburg, Leipziger Str. 44, 39120 Magdeburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Johann","family":"Bauer","sequence":"additional","affiliation":[{"name":"Max Planck Institute of Biochemistry, Martinsried, Am Klopferspitz 18, 82152 Planegg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Janne E.","family":"Reseland","sequence":"additional","affiliation":[{"name":"Clinical Oral Research Laboratory, Institute of Clinical Dentistry, UiO, University of Oslo, Geitmyrsveien 71 0455 Oslo, Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manfred","family":"Infanger","sequence":"additional","affiliation":[{"name":"Clinic for Plastic, Aesthetic and Hand Surgery, Otto von Guericke University Magdeburg, Leipziger Str. 44, 39120 Magdeburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aina","family":"Mari Lian","sequence":"additional","affiliation":[{"name":"Clinical Oral Research Laboratory, Institute of Clinical Dentistry, UiO, University of Oslo, Geitmyrsveien 71 0455 Oslo, Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elvis","family":"Okoro","sequence":"additional","affiliation":[{"name":"Osteoimmunology and Integrative Physiology Laboratory, Department of Biology, Texas Southern University, Cleburne, Houston, TX 77004, 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