Extracellular Matrix Proteins and Transcription of Matrix-Associated Genes in Mesenchymal Stromal Cells during Modeling
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x Proteins and Transcription of Matrix-Associated Genes in Mesenchymal Stromal Cells during Modeling of the Effects of Microgravity
I. V. Zhivodernikov, A. Yu. Ratushnyy, D. K. Matveeva, and L. B. Buravkova Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 170, No. 8, pp. 201-204, August, 2020 Original article submitted March 12, 2020 We studied the effects of simulated microgravity (10 days) on the production of extracellular matrix proteins and expression of extracellular matrix-associated genes in human mesenchymal stem cells. A decrease in collagen production, reduced expression of TIMP-1, TIMP-3, and MMP-11 genes, and enhanced expression of tenascin and laminin subunit were revealed. The results attest to activation of proteolytic processes in the matrix of mesenchymal stromal cells and weakening of cell adhesion to extracellular matrix under conditions of simulated microgravity. Key Words: mesenchymal stromal cells; extracellular matrix; simulated microgravity Prolonged exposure to microgravity during long-duration space flights is known to induce osteopenia and osteoporosis due to accelerated bone resorption and reduced osteoblast activity [4]. Mesenchymal stromal cells (MSC) are precursors of osteoblasts and osteocytes and can take part in the realization of the negative effect of weightlessness on the bone tissue. It is known that microgravity weakens the osteogenic differentiation of MSC shifting the equilibrium towards adipogenic committing [2,7]. The revealed functional changes are accompanied by transcriptional changes that can differ in different cell types and depend on the duration of exposure [11]. Gravity deprivation modifies expression of the genes of the cytoskeleton that undergoes remodeling under conditions of gravitational unloading [1] and genes of the extracellular matrix (ECM) [9] that consists of several tens of components. ECM, a mechanical framework of the tissue, deposits growth factors and other bioactive substances ensuring their stable concentration or release during degradation. ECM State Scientific Center of the Russian Federation — Institute of Biomedical Problems, Russian Academy of Sciences, Moscow, Russia. Address for correspondence: [email protected]. I. V. Zhivodernikov
macromolecules can be divided into fibrillar (collagen, fibronectin, and elastin) that form tissue framework and amorphous (proteoglycans and glycoproteins) that fill the space between fibers and cells [5,13]. ECM is not static; external and internal factors can change the ratio of components and their spatial orientation change. In each case, the specific profile of ECM depends on the balance of synthetic and proteolytic activities of cells [3, 12]. The aim of this work was to assess the effect of modeled microgravity on the ratio of collagen and non-collagen components of ECM and expression of genes of matrix-associated proteins.
MATERIALS AND METHODS Cellular effects of microgravity were modeled by 3D clinostating in a random positioning machine (RPM), a device that rotates in 2
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