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Nutraceuticals Synergistically Promote Osteogenesis in Cultured 7F2 Osteoblasts and Mitigate Inhibition of Differentiation and Maturation in Simulated Microgravity.

ABSTRACT: Microgravity is known to impact bone health, similar to mechanical unloading on Earth. In the absence of countermeasures, bone formation and mineral deposition are strongly inhibited in Space. There is an unmet need to identify nutritional countermeasures. Curcumin and carnosic acid are phytonutrients with anticancer, anti-inflammatory, and antioxidative effects and may exhibit osteogenic properties. Zinc is a trace element essential for bone formation. We hypothesized that these nutraceuticals could counteract the microgravity-induced inhibition of osteogenic differentiation and function. To test this hypothesis, we cultured 7F2 murine osteoblasts in simulated microgravity (SMG) in a Random Positioning Machine in the presence and absence of curcumin, carnosic acid, and zinc and evaluated cell proliferation, function, and differentiation. SMG enhanced cell proliferation in osteogenic medium. The nutraceuticals partially reversed the inhibitory effects of SMG on alkaline phosphatase (ALP) activity and did not alter the SMG-induced reduction in the expression of osteogenic marker genes in osteogenic medium, while they promoted osteoblast proliferation and ALP activity in the absence of traditional osteogenic media. We further observed a synergistic effect of the intermix of the phytonutrients on ALP activity. Intermixes of phytonutrients may serve as convenient and effective nutritional countermeasures against bone loss in space.

SUBMITTER: Braveboy-Wagner J

PROVIDER: S-EPMC8745420 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Conditioned media from endothelial progenitor cells cultured in simulated microgravity promote angiogenesis and bone fracture healing.

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| S-EPMC7792074 | biostudies-literature

Antioxidant Strategy to Prevent Simulated Microgravity-Induced Effects on Bone Osteoblasts.

Project description:The effects induced by microgravity on human body functions have been widely described, in particular those on skeletal muscle and bone tissues. This study aims to implement information on the possible countermeasures necessary to neutralize the oxidative imbalance induced by microgravity on osteoblastic cells. Using the model of murine MC3T3-E1 osteoblast cells, cellular morphology, proliferation, and metabolism were investigated during exposure to simulated microgravity on a random positioning machine in the absence or presence of an antioxidant-the 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid (Trolox). Our results confirm that simulated microgravity-induced morphological and metabolic alterations characterized by increased levels of reactive oxygen species and a slowdown of the proliferative rate. Interestingly, the use of Trolox inhibited the simulated microgravity-induced effects. Indeed, the antioxidant-neutralizing oxidants preserved cell cytoskeletal architecture and restored cell proliferation rate and metabolism. The use of appropriate antioxidant countermeasures could prevent the modifications and damage induced by microgravity on osteoblastic cells and consequently on bone homeostasis.

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Project description:Collagen produced in vitro by bone cells isolated from 19 patients with different forms of osteogenesis imperfecta (OI) was analysed. Clinically, four patients were classified as OI type I, 10 patients as OI type III and five patients as OI type IV. Bone cells of 12 of the 19 OI patients produced structurally abnormal type I collagen. Electrophoretically uniformly slower migrating collagen type I alpha-chains were found in one case of OI type I, in seven cases of OI type III and in one case of OI type IV; two cultures of OI type III produced two different populations of collagen type I alpha-chains, and one culture of OI type IV showed reduction-sensitive dimer formation of alpha 1(I) chains, resulting from the inadequate incorporation of a cysteine residue into the triple helical domain of alpha 1(I). Quantitative analysis of collagen metabolism led to the distinction of two groups of cultured OI osteoblasts. In osteoblasts of OI type I, mainly production of collagen was decreased, whereas secretion, processing and pericellular accumulation of (pro)collagen type I was similar to that in control osteoblasts. In contrast, in osteoblasts of OI types III and IV, production as well as secretion, processing and pericellular accumulation of (pro)collagen type I were significantly decreased. Low levels of type I collagen were found irrespective of the presence or absence of structural abnormalities of collagen type I in all OI types.

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Simulated microgravity induces a cellular regression of the mature phenotype in human primary osteoblasts.

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| S-EPMC5945613 | biostudies-literature

Transcription profiling of mouse osteoblasts under static vs simulated microgravity

Project description:The below table includes a smaller list of data that was analyzed by dChip and filtered by pvalue such that a file with about 4600 genes was obtained, which allowed for ease of use from 40,000 genes. Experiment Overall Design: The total RNA was extracted from 2T3 pre-osteoblast cells exposed to static or simulated microgravity (Rotating Wall Vessel) conditions. The RNA was then sent to Affymetrix microarray core facility at Baylor College of Medicine (Houston, TX) for microarray analysis.

2008-06-13 | E-GEOD-4658 | biostudies-arrayexpress

Bioinspired Scaffold Action Under the Extreme Physiological Conditions of Simulated Space Flights: Osteogenesis Enhancing Under Microgravity.

Project description:Prolonged exposure to microgravity (MG) during long-duration space flights is known to induce severe dysregulation of osteoblast functions connected to a significant bone loss, similar to the condition induced by osteoporosis. Hence, we here present MG as a promising model to challenge the effectiveness of new scaffolds designed for bone regeneration in counteracting bone loss. To this end, we carried out an integrative study aimed to evaluate, in the extreme condition of Random Positioning Machine-simulated MG, the osteoinductive potential of nanocrystalline magnesium-doped hydroxyapatite/type I collagen composite scaffold (MHA/Coll), that we previously demonstrated to be an excellent tool for bone tissue engineering. Initially, to test the osteoinductive properties of our bioinspired-scaffold, MHA/Coll structure was fully characterized under MG condition and compared to its static counterpart. Human bone marrow-derived mesenchymal stem cells were used to investigate the scaffold biocompatibility and ability to promote osteogenic differentiation after long-duration exposure to MG (up to 21 days). The results demonstrate that the nanostructure of MHA/Coll scaffold can alleviate MG-induced osteoblast dysfunction, promoting cell differentiation along the osteogenic lineage, with a consequent reduction in the expression of the surface markers CD29, CD44, and CD90. Moreover, these findings were corroborated by the ability of MHA/Coll to induce the expression of genes linked to osteogenesis, including alkaline phosphatase and osteocalcin. This study confirmed MHA/Coll capabilities in promoting osteogenesis even in extreme long-term condition of MG, suggesting MG as an effective challenging model to apply in future studies to validate the ability of advanced scaffolds to counteract bone loss, facilitating their application in translational Regenerative Medicine and Tissue Engineering.

| S-EPMC7362936 | biostudies-literature

Simulated Microgravity Inhibits Differentiation and Alters Gene Expression Profiles of 2T3 Pre-osteoblasts

Project description:Exposure to microgravity causes bone loss in humans, and the underlying mechanism is believed to be at least partially due to a decrease in bone formation by osteoblasts. Here, we examined the hypothesis that microgravity changes osteoblast gene expression profiles, resulting in bone loss. For this study, we developed an in vitro system that simulates microgravity using the Random Positioning Machine (RPM) to study the effects of microgravity on 2T3 pre-osteoblast cells grown in gas-permeable culture disks. Exposure of 2T3 cells to simulated microgravity using RPM for up to 9 days significantly inhibited alkaline phosphatase activity, recapitulating an expected bone loss response, without altering cell proliferation and shape. Next, we carried out a DNA microarray analysis to determine the gene expression profile of 2T3 cells exposed to 3 days of simulated microgravity. Among 10,000 genes examined with the microarray, 88 were downregulated while 52 were upregulated significantly by simulated microgravity by more than two-fold in comparison to the static 1g condition. By using real-time PCR assays, we verified the microarray data using some of the expected genes. For example, we confirmed that microgravity induced downregulation of alkaline phosphatase, runt related transcription factor 2 (runx2), osteomodulin, and parathyroid hormone 1 receptor, while confirming upregulation of cathepsin K mRNAs. In addition to the changes of the expected genes, the microarray data identified many more genes. The identification of these gravisensitive genes provide an useful insight in generating further hypotheses regarding their roles not only in microgravity-induced bone loss, but also in general population of patients with similar pathologic conditions such as osteoporosis. Keywords: other

2004-05-07 | GSE1367 | GEO

Simulated microgravity induces nuclear translocation of Bax and BCL-2 in glial cultured C6 cells.

Project description:Alterations in the control of apoptotic processes were observed in cells during space flight or under simulated microgravity, the latter obtained with the 3D-Random Positioning Machine (3D-RPM). Usually the proteins Bax and Bcl-2, act as pro- or anti-apoptotic regulators. Here we investigated the effects of simulated microgravity obtained by the 3D-RPM on cell viability, localization and expression of Bax and Bcl-2 in cultures of glial cancerous cells. We observed for the first time a transient cytoplasmic/nuclear translocation of Bax and Bcl-2 triggered by changing gravity vector. Bax translocates into the nucleus after 1 h, is present simultaneously in the cytoplasm after 6 h and comes back to the cytoplasm after 24 h. Bcl-2 translocate into the nucleus only after 6 h and comes back to the cytoplasm after 24 h. Physiological meaning, on the regulation of apoptotic event and possible applicative outcomes of such finding are discussed.

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static vs simulated microgravity

2006-12-31 | GSE4658 | GEO

Cellular mechanotransduction of human osteoblasts in microgravity.

Project description:Astronauts experience significant and rapid bone loss as a result of an extended stay in space, making the International Space Station (ISS) the perfect laboratory for studying osteoporosis due to the accelerated nature of bone loss on the ISS. This prompts the question, how does the lack of load due to zero-gravity propagate to bone-forming cells, human fetal osteoblasts (hFOBs), altering their maturation to mineralization? Here, we aim to study the mechanotransduction mechanisms by which bone loss occurs in microgravity. Two automated experiments, 4 microfluidic chips capable of measuring single-cell mechanics of hFOBs via aspiration and cell spheroids incubated in pressure-controlled chambers, were each integrated into a CubeLab deployed to the ISS National Laboratory. For the first experiment, we report protrusion measurements of aspirated cells after exposure to microgravity at the ISS and compare these results to ground control conducted inside the CubeLab. Our analysis revealed slightly elongated protrusions for space samples compared to ground samples indicating softening of hFOB cells in microgravity. In the second experiment, we encapsulated osteoblast spheroids in collagen gel and incubated the samples in pressure-controlled chambers. We found that microgravity significantly reduced filamentous actin levels in the hFOB spheroids. When subjected to pressure, the spheroids exhibited increased pSMAD1/5/9 expression, regardless of the microgravity condition. Moreover, microgravity reduced YAP expression, while pressure increased YAP levels, thus restoring YAP expression for spheroids in microgravity. Our study provides insights into the influence of microgravity on the mechanical properties of bone cells and the impact of compressive pressure on cell behavior and signaling in space.

| S-EPMC10925314 | biostudies-literature

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