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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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NASA NTRS2017

The Effects of CDKN1a/p21 on Oxidative Stress and Mitochondrial Function During Long Duration Spaceflight

Broad tissue degeneration and the failure of normal tissue regenerative processes in microgravity because of mechanical unloading are increasing concerns for sustaining life in space as the duration of future flight missions increases. Work in our laboratory has identified normal adult stem cell-based tissue regenerative processes, such as the formation of new bone, cartilage, and immune cells, as being particularly sensitive to the stresses of mechanical unloading in microgravity. Our studies have also identified the inhibition of differentiation of marrow mesenchymal stem cells and activation of CDKN1ap21-mediated cell cycle arrest in proliferative osteoprecursor cells on the bone surface as potential mechanisms for spaceflight-induced skeletal changes. This finding, in combination with the role of CDKN1ap21 as a suppressor of mammalian tissue regeneration, suggests that this gene could be responsible for suppressing stem cell-based tissue regeneration in response to disuse. In this work, we hypothesized that CDKN1ap21 regulates regenerative bone formation in response to alterations in mechanical load and tested this hypothesis by studying the skeletal phenotype and stem cell regenerative ability of juvenile (4-11 weeks old) and adult (18 weeks-12 months old) p21 (--) knockout (KO) mice. Additionally, we analyzed bone micro-architectural properties, bone formation rates and differentiation capacity of bone marrow stem cells (BMSCs) from male and female KO mice exposed to hindlimb unloading (HU) for 15-30 days. We found that juvenile KO mice exhibited increased femoral trabecular and cortical bone formation, whilst three-point bending of the tibias from KO mice showed decreased bone stiffness. Conversely, adult KO mice exhibited no significant differences in micro-architectural properties compared to WT (wild-type) but woven bone structure was indicative of rapid bone remodeling. Furthermore, cortical bone properties showed similar characteristics to aged bone, including increased cross-sectional area and perimeter, whilst three-point bending showed increased stiffness and toughness. Interestingly, in-vitro, KO mice exhibited increased differentiation and mineralized nodule formation in osteoblastogenesis assays compared to WT. Preliminary results from CDKN1ap21 KO mice subjected to HU suggest altered sensitivity to mechanical unloading resulting in decreased cortical thickness compared to WT mice. However, KO mice subjected to short and long-duration HU show increased in-vitro differentiation potential of BMSCs to from form mature, mineral-forming osteoblasts, indicating maintenance of regenerative potential. Analysis of bone formation rates, cell proliferation rates and key genes of interest are currently underway. These results indicate a novel role for CDKN1ap21 in load-dependent osteoprogenitor proliferation and differentiation and that deletion of CDKN1ap21 results in an age-dependent release of osteoblast proliferation inhibition and increased bone formation and turnover.

Stem Cells↗

NASA NTRS2014

TBS (Trabecular Bone Score) Expands Understanding of Spaceflight Effects on the Lumbar Spine of Long Duration Astronauts

Background: Bone loss due to long-duration spaceflight has been characterized by both DXA and QCT serial scans. It is unclear if these spaceflight-induced changes in bone mineral density and structure result in increased fracture incidence. NASA astronauts currently fly on 5-6-month missions on the International Space Station (ISS) and at least one 12-month mission is planned. While NASA has measured areal BMD (by DXA) and volumetric BMD (by QCT), and has estimated hip strength (by finite element models of QCT data, no method has yet been used to examine bone microarchitecture from lumbar spine (LS). DXA scans are routinely performed pre- and post-flight on all ISS astronauts to follow BMD changes associated with space flight. Trabecular Bone Score (TBS) is a relatively new method that measures grey-scale-level texture information extracted from lumbar spine DXA images and correlates with 3D parameters of bone micro-architecture. We evaluated the ability of LS TBS to discriminate changes in astronauts who have flown on ISS missions and to determine if TBS can provide additional information compared to DXA. Methods: LS (L1-4) DXA scans from 51 astronauts (mean age, 47 +/- 4) were divided into 3 groups based on the exercise regimes performed while onboard the ISS. Pre-ARED (exercise using a load-limited resistive exercise device, <300lb), ARED (exercise with a high-load resistive exercise device, up to 600lb) and a Bisphos group (ARED exercise and a 70-mg alendronate tablet once a week before and during flight, starting 17 days before launch). DXA scans were performed and analyzed on a Hologic Discovery W using the same technician for the pre- and postflight scans. LSC for the LS in our laboratory is 0.025 g/cm2. TBS was performed at the Mercy Hospital, Cincinnati, Ohio on a similar Hologic computer. TBS precision was calculated from 16 comparable test subjects (0.0XX g/cm2). Data were preliminary analyzed using a paired, 2-tailed t-test for the difference between pre- and postflight means.

Sibonga, Jean D.↗

NASA NTRS2015

Bone Loss During Spaceflight: Available Models and Counter-Measures

There is ongoing concern for human health during spaceflights. Of particular interest is the uncoupling of bone remodeling and its resultant effect on calcium metabolism and bone loss. The calculated average loss of bone mineral density (BMD) is approximately 1-1.5% per month of spaceflight. The effect of decreased BMD on associated fractures in astronauts is not known. Currently on the International Space Station (ISS), bone loss is managed through dietary supplements and modifications and resistance exercise regimen. As the duration of space flights increases, a review of the current methods available for the prevention of bone loss is warranted. The goal of this project is to review and summarize recent studies that have focused on maintaining BMD during exposure to microgravity. Interventions were divided into physical (Table 1), nutritional (Table 2), or pharmacologic (Table 3) categories. Physical modalities included resistance exercise, low level vibration, and low intensity pulsed ultrasound. Nutritional interventions included altering protein, salt, and fat intake; and vitamin D supplementation. Pharmacologic interventions included the use of bisphosphonates and beta blockers. Studies reported outcomes based on bone density determined by DXA bone scan, micro-architecture of histology and microCT, and serum and urine markers of bone turnover. The ground analog models utilized to approximate osseous physiology in microgravity included human patients previously paralyzed or subjects confined to bedrest. Ground analog animal models include paralysis, immobilization and ovariectomies. As a result of the extensive research performed there is a multi-modality approach available for the management of BMD during spaceflight that includes resistance training, nutrition and dietary supplements. However, there is a paucity of literature describing a formalized tiered protocol to guide investigators through the progression from animal models to human patient ground analogs to experiments on the ISS. With regards to testing, further evaluation to determine the association between non-invasive tests and fracture during and after spaceflight needs to be performed.

Morris, Jonathan↗