Changes in Human Foetal Osteoblasts Exposed to the Random Positioning Machine and Bone Construct Tissue Engineering.
Vivek MannDaniela GrimmThomas J CorydonMarcus KrügerMarkus WehlandStefan RiwaldtJayashree SahanaSascha KoppJohann BauerJanne E ReselandManfred InfangerAina Mari LianElvis OkoroAlamelu SundaresanPublished in: International journal of molecular sciences (2019)
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.
Keyphrases
- induced apoptosis
- bone loss
- bone mineral density
- gene expression
- cell cycle arrest
- tissue engineering
- transforming growth factor
- bone regeneration
- endothelial cells
- rheumatoid arthritis
- signaling pathway
- clinical trial
- transcription factor
- endoplasmic reticulum stress
- genome wide
- epithelial mesenchymal transition
- postmenopausal women
- dna methylation
- gestational age
- randomized controlled trial
- cell death
- immune response
- mesenchymal stem cells
- small molecule
- machine learning
- pi k akt
- lymph node metastasis
- papillary thyroid
- cell proliferation
- induced pluripotent stem cells
- preterm birth
- drug induced