Effects of Spaceflight on Cells of Bone Marrow Origin

Özçivici, Engin

doi:10.4274/tjh.2012.0127

Cited by 22 publications

(20 citation statements)

References 75 publications

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“…Colon cancer cells show a similar cell cycle arrest at G1 when exposed to mechanical loads in shear form [ 38 ], perhaps signifying a global pattern for the mechanical regulation on cancer cells. Similarly, MCF-7 breast cancer cells cycle more and show increased proliferation during space-flight [ 39 ], a condition that induce constant unloading to cells [ 40 ]. Further, constant weightlessness on thyroid carcinoma cells is associated with events that increase extracellular matrix formation, metastatic spread with the inhibition of apoptosis [ 41 ].…”

Section: Discussionmentioning

confidence: 99%

Daily application of low magnitude mechanical stimulus inhibits the growth of MDA-MB-231 breast cancer cells in vitro

Olcum

Özçivici

2014

Cancer Cell Int

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IntroductionMechanical loads can regulate cell proliferation and differentiation at various stages of development and homeostasis. However, the extension of this regulatory effect of mechanical loads on cancer cells is largely unknown. Increased physical compliance is one of the key features of cancer cells, which may hamper the transmission of mechanical loads to these cells within tumor microenvironment. Here we tested whether brief daily application of an external low magnitude mechanical stimulus (LMMS), would impede the growth of MDA-MB-231 aggressive type breast cancer cells in vitro for 3 wks of growth.MethodsThe signal was applied in oscillatory form at 90 Hz and 0.15 g, a regimen that would induce mechanical loads on MDA-MB-231 cells via inertial properties of cells rather than matrix deformations. Experimental cells were exposed to LMMS 15 min/day, 5 days/week in ambient conditions while control cells were sham loaded. Cell proliferation, viability, cycle, apoptosis, morphology and migration were tested via Trypan Blue dye exclusion, MTT, PI, Annexin V, Calcein-AM and phalloidin stains and scratch wound assays.ResultsCompared to sham controls, daily application of LMMS reduced the number and viability of cancerous MDA-MB-231 cells significantly after first week in the culture, while non-cancerous MCF10A cells were found to be unaffected. Flow cytomety analyses suggested that the observed decrease for the cancer cells in the LMMS group was due to a cell cycle arrest rather than apoptosis. LMMS further reduced cancer cell circularity and increased cytoskeletal actin in MDA-MB-231 cells.ConclusionCombined, results suggest that direct application of mechanical loads negatively regulate the proliferation of aggressive type cancer cells. If confirmed, this non-invasive approach may be integrated to the efforts for the prevention and/or treatment of cancer.

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Section: Discussionmentioning

confidence: 99%

Daily application of low magnitude mechanical stimulus inhibits the growth of MDA-MB-231 breast cancer cells in vitro

Olcum

Özçivici

2014

Cancer Cell Int

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“…The skeleton also serves as a mineral reservoir 4 , accommodates hematopoietic bone marrow 5 , and plays an active role in acid-base homeostasis 6 . Since many of these functions are affected by microgravity, including reduced mechanical loading 7 , altered calcium homeostasis 8 , reduced hematopoiesis 9 , and altered metabolism 10 , the relative contributions of different processes to bone loss in space remain unresolved. Bone health is assessed using imaging radiography, a technique that over time has developed from projection radiography, through single photon absorptiometry (SPA), to dual X-ray absorptiometry (DXA) and quantitative computed tomography (qCT) now widely used in a clinical setting 11 .…”

Section: Introductionmentioning

confidence: 99%

A systematic review and meta-analysis of bone loss in space travelers

et al. 2020

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Bone loss in space travelers is a major challenge for long-duration space exploration. To quantify microgravity-induced bone loss in humans, we performed a meta-analysis of studies systematically identified from searching Medline, Embase, Web of Science, BIOSIS, NASA Technical reports, and HathiTrust, with the last update in November 2019. From 25 articles selected to minimize the overlap between reported populations, we extracted post-flight bone density values for 148 individuals, and in-flight and postflight biochemical bone marker values for 124 individuals. A percentage difference in bone density relative to pre-flight was positive in the skull, +2.2% [95% confidence interval: +1.1, +3.3]; neutral in the thorax/upper limbs, −0.7% [−1.3, −0.2]; and negative in the lumbar spine/pelvis, −6.2 [−6.7, −5.6], and lower limbs, −5.4% [−6.0, −4.9]. In the lower limb region, the rate of bone loss was −0.8% [−1.1, −0.5] per month. Bone resorption markers increased hyperbolically with a time to half-max of 11 days [9, 13] and plateaued at 113% [108, 117] above pre-flight levels. Bone formation markers remained unchanged during the first 30 days and increased thereafter at 7% [5, 10] per month. Upon landing, resorption markers decreased to pre-flight levels at an exponential rate that was faster after longer flights, while formation markers increased linearly at 84% [39, 129] per month for 3-5 months post-flight. Microgravity-induced bone changes depend on the skeletal-site position relative to the gravitational vector. Post-flight recovery depends on spaceflight duration and is limited to a short post-flight period during which bone formation exceeds resorption.

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“…Superposition of mechanical signals onto habitual activity augments bone mass (SnowHarter et al, 1992), which may mitigate individual bone loss associated with aging, sedentary lifestyles, or space travel (Ozcivici et al, 2010a;Özcivici, 2013). Exogenous mechanical stimuli need not be comparable in magnitude to signals that are regularly experienced during habitual activity to be effective, as extremely low-magnitude (≤0.3 g, 1 g = 9.81 m/s 2 ) vibratory signals are also associated with anabolism in the bone through the activation of osteoblasts tissue when applied at high frequencies (>30 Hz) (Xie et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

Bone marrow stem cells adapt to low-magnitude vibrations by altering theircytoskeleton during quiescence and osteogenesis

Demiray¹,

Özçivici

2015

Turk J Biol

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Application of mechanical vibrations is anabolic to bone tissue, not only by guiding mature bone cells to increased formation, but also by increasing the osteogenic commitment of progenitor cells. However, the sensitivity and adaptive response of bone marrow stem cells to this loading regimen has not yet been identified. In this study, we subjected mouse bone marrow stem cell line D1-ORL-UVA to daily mechanical vibrations (0.15 g, 90 Hz, 15 min/day) for 7 days, both during quiescence and osteogenic commitment, to identify corresponding ultrastructural adaptations on cellular and molecular levels. During quiescence, mechanical vibrations significantly increased total actin content and actin fiber thickness, as measured by phalloidin staining and fluorescent microscopy. Cellular height also increased, as measured by atomic force microscopy, along with the expression of focal adhesion kinase (PTK2) mRNA levels. During osteogenesis, mechanical vibrations increased the total actin content, actin fiber thickness, and cytoplasmic membrane roughness, with significant increase in Runx2 mRNA levels. These results show that bone marrow stem cells demonstrate similar cytoskeletal adaptations to low-magnitude high-frequency mechanical loads both during quiescence and osteogenesis, potentially becoming more sensitive to additional loads by increased structural stiffness.

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Effects of Spaceflight on Cells of Bone Marrow Origin

Cited by 22 publications

References 75 publications

Daily application of low magnitude mechanical stimulus inhibits the growth of MDA-MB-231 breast cancer cells in vitro

Daily application of low magnitude mechanical stimulus inhibits the growth of MDA-MB-231 breast cancer cells in vitro

A systematic review and meta-analysis of bone loss in space travelers

Bone marrow stem cells adapt to low-magnitude vibrations by altering theircytoskeleton during quiescence and osteogenesis

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