Simulated Microgravity Remodels Extracellular Matrix of Osteocommitted Mesenchymal Stromal Cells

Abstract

The extracellular matrix (ECM) is the principal structure of bone tissue. Long-term spaceflights lead to osteopenia, which may be a result of the changes in composition as well as remodeling of the ECM by osteogenic cells. To elucidate the cellular effects of microgravity, human mesenchymal stromal cells (MSCs) and their osteocommitted progeny were exposed to simulated microgravity (SMG) for 10 days using random positioning machine (RPM). After RPM exposure, an imbalance of MSC collagen/non-collagen ratio at the expense of a decreased level of collagenous proteins was detected. At the same time, the secretion of proteases (cathepsin A, cathepsin D, MMP3) was increased. No significant effects of SMG on the expression of stromal markers and cell adhesion molecules on the MSC surface were noted. Upregulation of COL11A1, CTNND1, TIMP3, and TNC and downregulation of HAS1, ITGA3, ITGB1, LAMA3, MMP1, and MMP11 were detected in RPM exposed MSCs. ECM-associated transcriptomic changes were more pronounced in osteocommitted progeny. Thus, 10 days of SMG provokes a decrease in the collagenous components of ECM, probably due to the decrease in collagen synthesis and activation of proteases. The presented data demonstrate that ECM-associated molecules of both native and osteocommitted MSCs may be involved in bone matrix reorganization during spaceflight.

Heterotypic Cell Culture from Mouse Bone Marrow under Simulated Microgravity: Lessons for Stromal Lineage Functions

“…According to a semiquantitative colorimetric assay, the amounts of both collagenous and non-collagenous proteins were decreased following sμg ( p ≤ 0.05) ( Figure 3 A). Earlier studies have shown similar changes in collagenous and non-collagenous protein levels after 10 days of 3D clinorotation of MSCs from human adipose tissue [ 34 ]. In addition, a decrease in alkaline phosphatase activity and ECM in rat bone marrow MSCs and human MSCs was observed after 14 days of 3D clinorotation [ 19 , 35 , 36 ].…”

Long-Term Simulation of Microgravity Induces Changes in Gene Expression in Breast Cancer Cells

“…Under long-term µ g exposure, cancer cells depend on adhesion to evade cell death. Other cell types such as FTC-133 thyroid cancer cells and mesenchymal stromal cells showed a reduced ITGB1 gene expression when they were exposed to space or s-µ g conditions [ 64 , 69 ], whereas the ITGB1 mRNA was up-regulated in chondrocytes [ 70 ]. In summary, we discovered that the reaction of ITGB1 to environmental stresses such as µ g is cell-type-dependent and time-dependent.…”