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Pardo: Simulated microgravity using the Random Positioning Machine inhibits differentiation and alters gene expression profiles of 2T3 preosteoblasts

Discussion in 'Health News and Research unrelated to ME/CFS' started by WillowJ, Nov 10, 2018.

  1. WillowJ

    WillowJ Senior Member (Voting Rights)

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    Pardo, Steven J., Mamta J. Patel, Michelle C. Sykes, Manu O. Platt, Nolan L. Boyd, George P. Sorescu, Min Xu, Jack J. W. A. van Loon, May D. Wang, and Hanjoong Jo.

    Simulated microgravity using the Random Positioning Machine inhibits differentiation and alters gene expression profiles of 2T3 preosteoblasts.

    Am J Physiol Cell Physiol 288: C1211–C1221, 2005. First published February 2, 2005; doi:10.1152/ajpcell.00222.2004.

    Exposure to microgravity causes bone loss in humans, and the underlying mechanism is thought to be at least partially due to a decrease in bone formation by osteoblasts. In the present study, 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 preosteoblast cells grown in gas-permeable culture disks. Exposure of 2T3 cells to simulated microgravity using the RPM for up to 9 days significantly inhibited alkaline phosphatase activity, recapitulating a bone loss response that occurs in real microgravity conditions without altering cell proliferation and shape.

    Next, we performed DNA microarray analysis to determine the gene expression profile of 2T3 cells exposed to 3 days of simulated microgravity. Among 10,000 genes examined using the microarray, 88 were downregulated and 52 were upregulated significantly more than twofold using simulated microgravity com- pared with the static 1-g condition.

    We then verified the microarray data for some of the genes relevant in bone biology using real-time PCR assays and immunoblotting. We confirmed that microgravity downregulated levels of alkaline phosphatase, runt-related transcrip- tion factor 2, osteomodulin, and parathyroid hormone receptor 1 mRNA; upregulated cathepsin K mRNA; and did not significantly affect bone morphogenic protein 4 and cystatin C protein levels.

    The identification of gravisensitive genes provides useful insight that may lead to further hypotheses regarding their roles in not only micrograv- ity-induced bone loss but also the general patient population with similar pathological conditions, such as osteoporosis.

    https://www.physiology.org/doi/pdf/10.1152/ajpcell.00222.2004
     
    andypants likes this.
  2. WillowJ

    WillowJ Senior Member (Voting Rights)

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    “THERE IS INCREASING INTEREST in human space exploration, in- cluding extensive trips to deep-space planets such as Mars. However, the harsh outer space environment, consisting of microgravity and radiation, poses significant health risks for astronauts.

    “For example, microgravity conditions in space have been shown to cause decreased bone mass (5, 6, 9, 14), bone demineralization (7, 33, 36), skeletal muscle atrophy (23), cardiovascular deconditioning (2, 38), and immune dysfunc- tion (30).

    “Many of these pathophysiological changes cannot yet be counteracted adequately by physical exercise (18) or nutri- tional supplementation alone (6, 12, 34).“
     
  3. WillowJ

    WillowJ Senior Member (Voting Rights)

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    This would imply that microgravity is not directly comparable to deconditioning, if it can’t be cured by exercise.
     
  4. WillowJ

    WillowJ Senior Member (Voting Rights)

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    “Alkaline phosphatase, a known marker for bone formation, was downregulated fivefold below the static 1-g control using simulated microgravity. Runx2, a transcription factor regulat- ing osteocalcin levels, was downregulated 1.88-fold in micro- gravity compared with the static 1-g control condition. Para- thyroid hormone receptor 1 (pthr1), which acts directly on the skeleton to promote Ca2+ release from bone and on the kidney to enhance Ca2+ reabsorption, was downregulated fivefold by simulated microgravity.

    “On the other hand, inducers of osteo- lytic activity were also upregulated by simulated microgravity. For example, cathepsin K (ctsk) was upregulated 1.66-fold above the static 1-g control. Although the relative changes for runx2 and ctsk fall slightly below the twofold change threshold for significance, we think that both of these genes are poten- tially important in microgravity-induced genetic changes ob- served in 2T3 cells because of their established relevance in bone formation and resorption. Thus we also verified the microarray relative changes of these genes using RT-PCR.”
     

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