Impairment of 7F2 osteoblast function by simulated partial gravity in a Random Positioning Machine

Braveboy-Wagner, Justin; Lelkes, Peter I.

doi:10.1038/s41526-022-00202-x

Cited by 10 publications

(9 citation statements)

References 63 publications

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“…Braveboy-Wagner and Lelkes [ 163 ] used an RPM to simulate different partial gravity conditions comparable to the Moon, Mars, and “full” s-µ g ( Table 8 ). They studied the gene expression of the osteogenic markers ALPL , RUN , and ON in 7F2 osteoblasts cultured under different conditions and found that all three altered gravity levels induced a sharp decrease in the gene expression of all three markers.…”

Section: Resultsmentioning

confidence: 99%

“…However, in contrast to cell proliferation rates and alkaline phosphatase activities, which were also analyzed in this study, the gene expression changes were not dose-dependent, but all RPM conditions induced identical reductions. This hints towards a certain gravity threshold, which induces a more binary on–off switching of these genes [ 163 ].…”

Section: Resultsmentioning

confidence: 99%

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Current Knowledge about the Impact of Microgravity on Gene Regulation

Corydon

Schulz

Richter

et al. 2023

Cells

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Microgravity (µg) has a massive impact on the health of space explorers. Microgravity changes the proliferation, differentiation, and growth of cells. As crewed spaceflights into deep space are being planned along with the commercialization of space travelling, researchers have focused on gene regulation in cells and organisms exposed to real (r-) and simulated (s-) µg. In particular, cancer and metastasis research benefits from the findings obtained under µg conditions. Gene regulation is a key factor in a cell or an organism’s ability to sustain life and respond to environmental changes. It is a universal process to control the amount, location, and timing in which genes are expressed. In this review, we provide an overview of µg-induced changes in the numerous mechanisms involved in gene regulation, including regulatory proteins, microRNAs, and the chemical modification of DNA. In particular, we discuss the current knowledge about the impact of microgravity on gene regulation in different types of bacteria, protists, fungi, animals, humans, and cells with a focus on the brain, eye, endothelium, immune system, cartilage, muscle, bone, and various cancers as well as recent findings in plants. Importantly, the obtained data clearly imply that µg experiments can support translational medicine on Earth.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Current Knowledge about the Impact of Microgravity on Gene Regulation

Corydon

Schulz

Richter

et al. 2023

Cells

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“…Osteoblast‐specific genes include alkaline phosphatase, osteocalcin, and osteopontin, among others. [ 30 ] They are critical factors in the osteogenic differentiation of stem cells and bone development. [ 30 ] Runx2 is a specific transcriptional regulator of mesenchymal stem cell differentiation into osteoblasts.…”

Section: Resultsmentioning

confidence: 99%

“…[ 30 ] They are critical factors in the osteogenic differentiation of stem cells and bone development. [ 30 ] Runx2 is a specific transcriptional regulator of mesenchymal stem cell differentiation into osteoblasts. [ 31 ] Runx2 is the earliest and most specifically characterized marker gene of osteogenic differentiation.…”

Section: Resultsmentioning

confidence: 99%

PIP2 Alteration Caused by Elastic Modulus and Tropism of Electrospun Scaffolds Facilitates Altered BMSCs Proliferation and Differentiation

et al. 2023

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engineering and stem cell therapy. [3][4][5] There is increasing evidence that biomaterial surface topography is an essential factor that selectively influences cell adhesion and, in some cases, promotes cell differentiation. [6] To date, various biomaterials with different topographies at both the micrometer and nanometer scales, such as columns, grooves, and submicron fibers, have been applied to study the influence of topography on cellular functions. [7] Electrospun submicron fibers have been extensively explored as scaffolds to manipulate cell migration owing to their unique characteristics in mimicking the hierarchical architecture of the extracellular matrix. [8] In particular, aligned electrospun submicron fibers arrays can guide and promote the directional migration of cells. [9][10][11] Therefore, submicron fibers are widely applied to influence cell behavior. [12] Studies have indicated that fibroblasts on aligned substrates align themselves parallel with their substrate and increase production of the actin and focal adhesion-related genes. [13] Studies have stained neuronal differentiation marker proteins and found that neural stem cells aligned on submicron fibers had a higher differentiation rate than cells on random submicron fibers. [14] Although traditional molecular biology approaches have clearly shown that aligned submicron fibers can promote stem cell proliferation and differentiation, the mechanistic reasons for the differences between aligned and random fibers still need to be clarified. Since compositionally, dimensionally, geometrically, and morphologically controllable nanofibrous materials can be synthesized, many nanofibrous materials have been applied in biomedicine. [15,16] However, the hierarchical architecture structure is not destined to be designed into an aligned structure, leading to incomplete cell growth, a slow differentiation rate, and excessive waste of random materials. Therefore, it is essential to clarify the difference between the aligned and random structures and to reduce this difference.Researchers have found that miRNAs are essential factors in substance cell interactions. [17] MiRNAs are a class of endogenous noncoding small RNAs that bind to the 3′ untranslated regions of their target mRNAs, [18] leading to degradation or translational repression of these mRNAs, thereby regulating various cellular functions. [19] Recent studies have shown that miRNAs play Aligned submicron fibers have played an essential role in inducing stem cell proliferation and differentiation. In this study, it is aimed to identify the differential causes of stem cell proliferation and differentiation between bone marrow mesenchymal stem cells (BMSCs) on aligned-random fibers with different elastic modulus, and to change the differential levels through a regulatory mechanism mediated by B-cell lymphoma 6 protein(BCL-6) and miRNA-126-5p(miR-126-5p). The results showed that phosphatidylinositol(4,5)bisphosphate alterations are found in the aligned fibers compared with the random fibers, which ...

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“…In agreement, Hu and others found a significant reduction in osteoblastic differentiation and mineralized nodule formation in murine MC3T3-E1 preosteoblasts exposed to RPM for 24 h, in association with reduced expression of certain differentiation markers, such as runt-related transcription factor 2 (RUNX2), osteocalcin (OCN) and type I collagen ( Hu et al, 2015 ). Finally, the inhibitory effects of microgravity on osteoblast function have recently been confirmed by Braveboy-Wagner and Lelkes, who observed that exposure of 7F2 osteoblasts to various levels of simulated partial gravity resulted in a significant gravity-dependent inhibition of short-term (6 days) proliferation and alkaline phosphatase (ALP) activity and long-term (21 days) mineralization, suggesting a close association between impaired cell function and simulated partial gravity levels ( Braveboy-Wagner and Lelkes, 2022 ). However, despite numerous research efforts in recent years, the mechanisms by which weightlessness causes high bone resorption and a rapid decrease in bone minerals and calcium are largely unknown, as is the knowledge about the role of potential markers in microgravity-dependent bone tissue loss.…”

Section: Introductionmentioning

confidence: 83%

Recombinant irisin prevents cell death and mineralization defects induced by random positioning machine exposure in primary cultures of human osteoblasts: A promising strategy for the osteoporosis treatment

et al. 2023

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Spaceflight exposure, like prolonged skeletal unloading, is known to result in significant bone loss, but the molecular mechanisms responsible are still partly unknown. This impairment, characterizing both conditions, suggests the possibility of identifying common signalling pathways and developing innovative treatment strategies to counteract the bone loss typical of astronauts and osteoporotic patients. In this context, primary cell cultures of human osteoblasts derived from healthy subjects and osteoporotic patients were exposed to random positioning machine (RPM) to reproduce the absence of gravity and to exacerbate the pathological condition, respectively. The duration of exposure to RPM was 3 or 6 days, with the aim of determining whether a single administration of recombinant irisin (r-irisin) could prevent cell death and mineralizing capacity loss. In detail, cellular responses were assessed both in terms of death/survival, by MTS assay, analysis of oxidative stress and caspase activity, as well as the expression of survival and cell death proteins, and in terms of mineralizing capacity, by investigating the pentraxin 3 (PTX3) expression. Our results suggest that the effects of a single dose of r-irisin are maintained for a limited time, as demonstrated by complete protection after 3 days of RPM exposure and only partial protection when RPM exposure was for a longer time. Therefore, the use of r-irisin could be a valid strategy to counteract the bone mass loss induced by weightlessness and osteoporosis. Further studies are needed to determine an optimal treatment strategy based on the use of r-irisin that is fully protective even over very long periods of exposure and/or to identify further approaches to be used in a complementary manner.

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Impairment of 7F2 osteoblast function by simulated partial gravity in a Random Positioning Machine

Cited by 10 publications

References 63 publications

Current Knowledge about the Impact of Microgravity on Gene Regulation

Current Knowledge about the Impact of Microgravity on Gene Regulation

PIP2 Alteration Caused by Elastic Modulus and Tropism of Electrospun Scaffolds Facilitates Altered BMSCs Proliferation and Differentiation

Recombinant irisin prevents cell death and mineralization defects induced by random positioning machine exposure in primary cultures of human osteoblasts: A promising strategy for the osteoporosis treatment

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