Space Flight Calcium: Implications for Astronaut Health, Spacecraft Operations, and Earth

Smith, Scott M.; McCoy, Torin; Gazda, Daniel B.; Morgan, JL; Heer, Martina; Zwart, Sara R.

doi:10.3390/nu4122047

Cited by 65 publications

(45 citation statements)

References 96 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It has been reported that calcium signaling directly stimulates autophagy [31,32] and PLCγ2 is involved in the regulation of intracellular Ca 2+ level [33]. It has also been shown that space flight increases calcium release from bone [39]. Our findings that microgravity conditions increase PLCγ2 expression suggest that the PLCγ2/calcium signaling pathway modulates autophagy during OCL differentiation.…”

Section: Discussionsupporting

confidence: 63%

Microgravity control of autophagy modulates osteoclastogenesis

Sambandam

Townsend

et al. 2014

Bone

View full text Add to dashboard Cite

Evidence indicates that astronauts experience significant bone loss during space mission. Recently, we used the NASA developed rotary cell culture system (RCCS) to simulate microgravity (μXg) conditions and demonstrated increased osteoclastogenesis in mouse bone marrow cultures. Autophagy is a cellular recycling process of nutrients. Therefore, we hypothesize that μXg control of autophagy modulates osteoclastogenesis. Real-time PCR analysis of total RNA isolated from mouse bone marrow derived non-adherent cells subjected to modeled μXg showed a significant increase in autophagic marker Atg5, LC3 and Atg16L mRNA expression compared to ground based control (Xg) cultures. Western blot analysis of total cell lysates identified an 8.0-fold and 7.0-fold increase in the Atg5 and LC3-II expression, respectively. Confocal microscopy demonstrated an increased autophagosome formation in μXg subjected RAW 264.7 preosteoclast cells. RT2 profiler PCR array screening for autophagy related genes identified that μXg upregulates intracellular signaling molecules associated with autophagy, autophagosome components and inflammatory cytokines/growth factors which coregulate autophagy in RAW 264.7 preosteoclast cells. Autophagy inhibitor, 3-methyladenine (3-MA) treatment of mouse bone marrow derived non-adherent mononuclear cells showed a significant decrease in μXg induced Atg5 and LC3 mRNA expression in the presence or absence of RANK ligand (RANKL) stimulation. Furthermore, RANKL treatment significantly increased (8-fold) p-CREB transcription factor levels under μXg as compared to Xg cultures and 3-MA inhibited RANKL increased p-CREB expression in these cells. Also, 3-MA suppresses μXg elevated osteoclast differentiation in mouse bone marrow cultures. Thus, our results suggest that μXg induced autophagy plays an important role in enhanced osteoclast differentiation and could be a potential therapeutic target to prevent bone loss in astronauts during space flight missions.

show abstract

Section: Discussionsupporting

confidence: 63%

Microgravity control of autophagy modulates osteoclastogenesis

Sambandam

Townsend

et al. 2014

Bone

View full text Add to dashboard Cite

show abstract

“…Serum total calcium and urinary calcium were determined by atomic absorption spectrophotometry (PerkinElmer, Waltham, MA, 1.86% within‐ and 2.52% between‐assay CVs, CAP proficiency testing) (Smith et al. ,b, , , ,c, ; Zwart et al. , ), and whole‐blood ionized calcium (<1% CV) was determined using a portable analyzer (i‐STAT ® 1 Analyzer, i‐STAT, East Windsor, NJ; between‐assay CV for ionized Ca = 1.15%) (Smith et al.…”

Section: Methodsmentioning

confidence: 99%

Sex‐specific responses of bone metabolism and renal stone risk during bed rest

Morgan

Heer

Hargens

et al. 2014

Physiological Reports

Self Cite

View full text Add to dashboard Cite

The purpose of this study was to directly assess sex differences in bone loss, bone biochemistry, and renal stone risk in bed rest. Bed rest simulates some spaceflight effects on human physiology and can be used to address the potential existence of sex‐specific effects on bone metabolism and renal stone risk in space. We combined data from the control subjects in five head‐down‐tilt bed rest studies (combined n = 50 men, 24 women) of differing durations (14–90 days). All subjects were healthy volunteers. Mean age was 35 ± 9 years for women and 33 ± 8 years for men. The main outcome measures were bone density and biochemistry, and renal stone risk chemistry. Before bed rest began, men had higher bone mineral density and content (P < 0.001), and excreted more biomarkers of bone resorption and calcium per day than did women (P < 0.05). These differences remained during bed rest. A number of urine chemistry analytes increased (e.g., calcium) or decreased (e.g., sodium, citrate, and urine volume) significantly for men and women during bed rest. These changes may predispose men to higher stone risk. Men and women do not have substantially different responses to the skeletal unloading of bed rest.

show abstract

“…The endocrine counter-regulatory mechanisms to maintain normal serum calcium are a reduction in serum parathyroid hormone (PTH) and consequently lower 1,25-dihydroxyvitamin D concentrations (23). However, PTH is also a known potent regulator of SOST/sclerostin in osteocytes both in humans and in animal models (25,26), raising the possibility that the increase in SOST/sclerostin during unloading or bed rest might be a consequence of decreased serum PTH rather than direct mechanical sensing by osteocytes.…”

mentioning

confidence: 94%

“…Regardless of the initiation mechanisms, the hallmark of immobilization and microgravity in humans is an increase in bone resorption (23,24), resulting in subsequent transient hypercalcemia with persistently increased urinary and fecal calcium loss (23). The endocrine counter-regulatory mechanisms to maintain normal serum calcium are a reduction in serum parathyroid hormone (PTH) and consequently lower 1,25-dihydroxyvitamin D concentrations (23).…”

mentioning

confidence: 99%

The Wnt Inhibitor Sclerostin Is Up-regulated by Mechanical Unloading in Osteocytes in Vitro

Spatz

Wein

Gooi

et al. 2015

Journal of Biological Chemistry

257

261

View full text Add to dashboard Cite

Background: Recent studies have suggested osteocytes as key players in mechanosensation and skeletal metabolism. Results: Simulated microgravity induces an autonomous up-regulation of SOST/sclerostin and RANKL/OPG in a novel osteocytic cell line, Ocy454. Conclusion: Mechanical loading regulates intrinsic osteocyte responses in concert with hormonal and cytokine inputs. Significance: Learning how osteocytes sense mechanical loads would enable novel interventions to prevent disuse-induced bone loss.

show abstract

Space Flight Calcium: Implications for Astronaut Health, Spacecraft Operations, and Earth

Cited by 65 publications

References 96 publications

Microgravity control of autophagy modulates osteoclastogenesis

Microgravity control of autophagy modulates osteoclastogenesis

Sex‐specific responses of bone metabolism and renal stone risk during bed rest

The Wnt Inhibitor Sclerostin Is Up-regulated by Mechanical Unloading in Osteocytes in Vitro

Contact Info

Product

Resources

About