Simulated Microgravity Remodels Extracellular Matrix of Osteocommitted Mesenchymal Stromal Cells

Zhivodernikov, I. V.; Ratushnyy, A. Yu.; Буравкова, Л. Б.

doi:10.3390/ijms22115428

Cited by 11 publications

(4 citation statements)

References 69 publications

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“…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 ].…”

Section: Resultsmentioning

confidence: 78%

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

Markina,

Tyrina,

Ratushnyy

et al. 2023

IJMS

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Muscle and skeleton structures are considered most susceptible to negative factors of spaceflights, namely microgravity. Three-dimensional clinorotation is a ground-based simulation of microgravity. It provides an opportunity to elucidate the effects of microgravity at the cellular level. The extracellular matrix (ECM) content, transcriptional profiles of genes encoding ECM and remodelling molecules, and secretory profiles were investigated in a heterotypic primary culture of bone marrow cells after 14 days of 3D clinorotation. Simulated microgravity negatively affected stromal lineage cells, responsible for bone tissue formation. This was evidenced by the reduced ECM volume and stromal cell numbers, including multipotent mesenchymal stromal cells (MSCs). ECM genes encoding proteins responsible for matrix stiffness and cell-ECM contacts were downregulated. In a heterotypic population of bone marrow cells, the upregulation of genes encoding ECM degrading molecules and the formation of a paracrine profile that can stimulate ECM degradation, may be mechanisms of osteodegenerative events that develop in real spaceflight.

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Section: Resultsmentioning

confidence: 78%

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

Markina,

Tyrina,

Ratushnyy

et al. 2023

IJMS

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“…Our study found that HWJMSC-EVs increased the expression of ITGB1 in chondrocytes and hBMSCs. The key role of ITGB1 in cell migration, proliferation [41], and adhesion [42] has been reported, and the TGF-β/Smad2/3 pathway is known for its ability to inhibit cell apoptosis, promote tissue regeneration [43], and promote the proliferation and differentiation of MSCs and chondrocytes [44,45]. In addition, the TGF-β/Smad2/3 pathway plays an important role in cartilage degeneration [46], maintenance of cartilage and the ECM [29,47], and inhibition of the progression of osteoarthritis [48].…”

Section: Discussionmentioning

confidence: 99%

HWJMSC-EVs promote cartilage regeneration and repair via the ITGB1/TGF-β/Smad2/3 axis mediated by microfractures

Chen,

Zhou,

Luo

et al. 2024

J Nanobiotechnol

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The current first-line treatment for repairing cartilage defects in clinical practice is the creation of microfractures (MF) to stimulate the release of mesenchymal stem cells (MSCs); however, this method has many limitations. Recent studies have found that MSC-derived extracellular vesicles (MSC-EVs) play an important role in tissue regeneration. This study aimed to verify whether MSC-EVs promote cartilage damage repair mediated by MFs and to explore the repair mechanisms. In vitro experiments showed that human umbilical cord Wharton’s jelly MSC-EVs (hWJMSC-EVs) promoted the vitality of chondrocytes and the proliferation and differentiation ability of bone marrow-derived MSCs. This was mainly because hWJMSC-EVs carry integrin beta-1 (ITGB1), and cartilage and bone marrow-derived MSCs overexpress ITGB1 after absorbing EVs, thereby activating the transforming growth factor-β/Smad2/3 axis. In a rabbit knee joint model of osteochondral defect repair, the injection of different concentrations of hWJMSC-EVs into the joint cavity showed that a concentration of 50 µg/ml significantly improved the formation of transparent cartilage after MF surgery. Extraction of regenerated cartilage revealed that the changes in ITGB1, transforming growth factor-β, and Smad2/3 were directly proportional to the repair of regenerated cartilage. In summary, this study showed that hWJMSC-EVs promoted cartilage repair after MF surgery. Graphical abstract

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“…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.…”

Section: Discussionmentioning

confidence: 99%

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

Sahana

Cortés-Sánchez

Sandt

et al. 2023

IJMS

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Microgravity changes the gene expression pattern in various cell types. This study focuses on the breast cancer cell lines MCF-7 (less invasive) and MDA-MB-231 (triple-negative, highly invasive). The cells were cultured for 14 days under simulated microgravity (s-µg) conditions using a random positioning machine (RPM). We investigated cytoskeletal and extracellular matrix (ECM) factors as well as focal adhesion (FA) and the transmembrane proteins involved in different cellular signaling pathways (MAPK, PAM and VEGF). The mRNA expressions of 24 genes of interest (TUBB, ACTB, COL1A1, COL4A5, LAMA3, ITGB1, CD44, VEGF, FLK1, EGFR, SRC, FAK1, RAF1, AKT1, ERK1, MAPK14, MAP2K1, MTOR, RICTOR, VCL, PXN, CDKN1, CTNNA1 and CTNNB1) were determined by quantitative real-time PCR (qPCR) and studied using STRING interaction analysis. Histochemical staining was carried out to investigate the morphology of the adherent cells (ADs) and the multicellular spheroids (MCSs) after RPM exposure. To better understand this experimental model in the context of breast cancer patients, a weighted gene co-expression network analysis (WGCNA) was conducted to obtain the expression profiles of 35 breast cell lines from the HMS LINCS Database. The qPCR-verified genes were searched in the mammalian phenotype database and the human genome-wide association studies (GWAS) Catalog. The results demonstrated the positive association between the real metastatic microtumor environment and MCSs with respect to the extracellular matrix, cytoskeleton, morphology, different cellular signaling pathway key proteins and several other components. In summary, the microgravity-engineered three-dimensional MCS model can be utilized to study breast cancer cell behavior and to assess the therapeutic efficacies of drugs against breast cancer in the future.

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Simulated Microgravity Remodels Extracellular Matrix of Osteocommitted Mesenchymal Stromal Cells

Cited by 11 publications

References 69 publications

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

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

HWJMSC-EVs promote cartilage regeneration and repair via the ITGB1/TGF-β/Smad2/3 axis mediated by microfractures

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

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