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Effects of microgravity on osteoblast growth

Studies from space flights over the past two decades have demonstrated that basic physiological changes occur in humans during space flight. These changes include cephalic fluid shifts, loss of fluid and electrolytes, loss of muscle mass, space motion sickness, anemia, reduced immune response, and loss of calcium and mineralized bone. The cause of most of these manifestations is not known and until recently, the general approach was to investigate general systemic changes, not basic cellular responses to microgravity. Recently analyzed data from the 1973-1974 Skylabs disclose that there is a rise in the systemic hormone, cortisol, which may play a role in bone loss in flight. In two flights where bone growth was measured (Skylabs 3 and 4), the crew members had a significant loss of calcium accompanied by a rise in 24 hour urinary cortisol during the entire flight period. In ground-based work on osteoblasts, we have demonstrated that equivalent amounts of glucocorticoids can inhibit osteoblast cell growth. In addition, this laboratory has recently studied gene growth and activation of mouse osteoblasts (MC3T3-E1) during spaceflight. Osteoblast cells were grown on glass coverslips, loaded in the Biorack plunger boxes 18 hours before launch and activated 19 hours after launch in the Biorack incubator under microgravity conditions. The osteoblasts were launched in a serum deprived state, activated and collected in microgravity. Samples were collected at 29 hours after sera activation (0-g, n=4; 1-g, n=4). The osteoblasts were examined for changes in gene expression and cell morphology. Approximately one day after growth activation, remarkable differences were observed in gene expression in 0-g and 1-g flight samples. The 0-g activated cells had increased c-fos mRNA when compared to flight 1-g controls. The message of immediate early growth gene, cox-2 was decreased in the microgravity activated cells when compared to ground or 1-g flight controls. Cox-1 was not detected in any of the samples. There were no significant differences in the expression of actin mRNA between the 0-g and 1-g samples. These data indicate that quiescent osteoblasts are slower to enter the cell cycle in microgravity, suggesting that the force of gravity itself may be a significant factor in bone loss in spaceflight. Preliminary data from our STS 76 flight experiment support our hypothesis that a basic biological response occurs at the tissue, cellular, and molecular level in 0-g. Here we examine ground-based and space flown data on osteoblast growth in ground-based experiments mimicking space flight conditions and in microgravity to simulate lack of gravity stress to help us understand the mechanism of bone loss by experiments.

NASA Experiment Number 9403056

NASA: 60 Years and Counting...

Sputnik launched on 4 Oct 1057. On July 29, 1958, Eisenhower signed the National Aeronautics and Space Act, the creation of NASA. The Soviets launched the first human into orbit, Yuri Gagarin, on April 12, 1961. On 5 May 1961, Alan Shepard's Freedom 7 Mercury capsule lifted off at 9:34 a.m. from Launch Complex 5 at Cape Canaveral Air Force Station, and flew a suborbital trajectory lasting 15 minutes and 22 seconds, America's first man in space. On 25 May 1961, Kennedy delivered a speech to a joint session of Congress. In that speech, he stated "I believe that this nation should commit itself to achieving the goal, before this decade is out, of landing a man on the moon and returning him safely to the earth." The rest, as they say, is history. Project Mercury, the first U.S. program to put humans in space, made 25 flights, six of which carried astronauts between 1961 and 1963. The Gemini program primarily tested equipment and mission procedures and trained astronauts and ground crews for future Apollo missions to the Moon. Exactly eight years, one month and 26 days after President Kennedy challenged Americans to reach for the Moon, Project Apollo landed the first humans on the lunar surface and returned them safely to Earth. In 1973, Skylab expeditions paved the way for the International Space Station. Over 30 years, NASA's space shuttle fleet, ”Columbia, Challenger, Discovery, Atlantis and Endeavour,” flew 135 missions and carried 355 different people to space. The space shuttle carried people into orbit repeatedly; launched, recovered and repaired satellites; conducted cutting-edge research; and built the largest structure in space, the International Space Station. Tragically, NASA lost two crews of seven in the 1986 Challenger accident and the 2003 Columbia accident. The International Space Station is a model for global cooperation and scientific advancements that is enabling growth of private industry in low-Earth orbit and development of new technologies to advance human space exploration. Built between 1998 and 2011, the space station has housed humans continuously since Nov. 2, 2000. NASA has contracted with commercial companies SpaceX, Orbital ATK, and Sierra Nevada Corporation to deliver science investigations, cargo, and supplies to the crews living in space, and soon Boeing and SpaceX will transport astronauts to and from the station. Today, NASA is working on many fronts to advance man's presence in space. NASA's Exploration Campaign will establish U.S. preeminence in cislunar space through the operations and the deployment of a U.S.-led Lunar Orbital Platform-Gateway (LOPG). Together with the Orion and SLS Programs, the LOPG is central to advancing and sustaining human space exploration goals, and is the unifying single stepping off point for human cislunar operations, lunar surface access and missions to Mars. As one might expect, EMC for all this activity is challenging, to say the least. In the next half-hour or so, I will talk about some of those challenges and how the different programs are meeting them.

Scully, Bob

Body mass, energy intake, and water consumption of rats and humans during space flight

Alteration of metabolism has been suggested as a major limiting factor to long-term space flight. In humans and primates, a negative energy balance has been reported. The metabolic response of rats to space flight has been suggested to result in a negative energy balance. We hypothesized that rats flown in space would maintain energy balance as indicated by maintenance of caloric intake and body mass gain. Further, the metabolism of the rat would be similar to that of laboratory-reared animals. We studied the results from 15 space flights lasting 4 to 19 d. There was no difference in average body weight (206 +/- 13.9 versus 206 +/- 14.8 g), body weight gain (5.8 +/- 0.48 versus 5.9 +/- 0.56 g/d), caloric intake (309 +/- 21.0 versus 309 +/- 20.1 kcal/kg of body mass per day), or water intake (200 +/- 8.6 versus 199 +/- 9.3 mL/kg of body mass per day) between flight and ground control animals. Compared with standard laboratory animals of similar body mass, no differences were noted. The observations suggested that the negative balance observed in humans and non-human primates may be due to other factors in the space-flight environment.

Non-NASA Center

Energy expenditure and balance during spaceflight on the space shuttle

The objectives of this study were as follows: 1) to measure human energy expenditure (EE) during spaceflight on a shuttle mission by using the doubly labeled water (DLW) method; 2) to determine whether the astronauts were in negative energy balance during spaceflight; 3) to use the comparison of change in body fat as measured by the intake DLW EE, 18O dilution, and dual energy X-ray absorptiometry (DEXA) to validate the DLW method for spaceflight; and 4) to compare EE during spaceflight against that found with bed rest. Two experiments were conducted: a flight experiment (n = 4) on the 16-day 1996 life and microgravity sciences shuttle mission and a 6 degrees head-down tilt bed rest study with controlled dietary intake (n = 8). The bed rest study was designed to simulate the flight experiment and included exercise. Two EE determinations were done before flight (bed rest), during flight (bed rest), and after flight (recovery). Energy intake and N balance were monitored for the entire period. Results were that body weight, water, fat, and energy balance were unchanged with bed rest. For the flight experiment, decreases in weight (2.6 +/- 0.4 kg, P < 0.05) and N retention (-2. 37 +/- 0.45 g N/day, P < 0.05) were found. Dietary intake for the four astronauts was reduced in flight (3,025 +/- 180 vs. 1,943 +/- 179 kcal/day, P < 0.05). EE in flight was 3,320 +/- 155 kcal/day, resulting in a negative energy balance of 1,355 +/- 80 kcal/day (-15. 7 +/- 1.0 kcal. kg-1. day-1, P < 0.05). This corresponded to a loss of 2.1 +/- 0.4 kg body fat, which was within experimental error of the fat loss determined by 18O dilution (-1.4 +/- 0.5 kg) and DEXA (-2.4 +/- 0.4 kg). All three methods showed no change in body fat with bed rest. In conclusion, 1) the DLW method for measuring EE during spaceflight is valid, 2) the astronauts were in severe negative energy balance and oxidized body fat, and 3) in-flight energy (E) requirements can be predicted from the equation: E = 1.40 x resting metabolic rate + exercise.

Non-NASA Center

The Effects of Microgravity on Seated Height (Spinal Elongation)

ABSTRACT Many physiological factors, such as spinal elongation, fluid shifts, bone atrophy, and muscle loss, occur during an exposure to a microgravity environment. Spinal elongation is just one of the factors that can also affect the safety and performance of a crewmember while in space. Spinal elongation occurs due to the lack of gravity/compression on the spinal column. This allows for the straightening of the natural spinal curve. There is a possible fluid shift in the inter-vertebral disks that may also result in changes in height. This study aims at collecting the overall change in seated height for crewmembers exposed to a microgravity environment. During previous Programs, Apollo-Soyuz Test Project (ASTP) and Skylab, spinal elongation data was collected from a small number of subjects in a standing posture but were limited in scope. Data from these studies indicated a quick increase in stature during the first few days of weightlessness, after which stature growth reached a plateau resulting in up to a 3% increase of the original measurement [1-5]. However, this data was collected only for crewmembers in standing posture and not in a seated posture. Seated height may have a different effect than standing height due to a change in posture as well as due to a compounded effect of wearing restraints and a potential compression of the gluteal area. Seated height was deemed as a critical measurement in the design of the Constellation Program s (CxP) Crew Exploration Vehicle (CEV), called Orion which is now the point-of-departure vehicle for the Multi-Purpose Crew Vehicle (MPCV) Program; therefore a better understanding of the effects of microgravity on seated height is necessary. Potential changes in seated height that may not have impacted crew accommodation in previous Programs will have significant effects on crew accommodation due to the layout of seats in the Orion.. The current and existing configuration is such that the four crewmembers are stacked two by two with the commander and pilot seats on the top and the two remaining seats underneath, thereby limiting the amount of clearance for the crewmembers seated in the bottom seat. The inner mold line of these types of vehicles are fixed due to other design constraints; therefore, it is essential that all seats incorporate additional clearance to account for adequate spinal growth thereby ensuring that the crew can safely ingress the seat and be strapped in prior to its return to earth. If there is not enough clearance to account for spinal growth deltas between seats then there is the potential that crewmembers will not be able to comfortably and safely fit into their seats. The crewmember in the bottom stacked seat may even have negative clearance with the seat above him or her which could lead to potential ingress/egress issues or potentially injury of the crewmember during landing. These impacts are specific to these types of vehicles with stacked seat configuration. Without proper knowledge of the amount of spinal elongation, or growth, which occurs due to microgravity and space flight, the design of future vehicle(s) or suits may cause injury, discomfort, and limit crew accommodation and crew complements. The experiment primarily aimed to collect seated height data for subjects exposed to microgravity environments, and feed new information regarding the effect of elongation of the spine forward into the design of the Orion. The data collected during the experiment included, two seated height measurement and two digital pictures of seated height pre-, in-, and post-flight. In addition to seated height, crewmembers had an optional task of collecting stature , standing height. Seated height data was obtained from 29 crewmembers that included 8 ISS increment crew (2 females and 6 males) and 21 Shuttle crew (1 female, 20 males), and whose mean age was 48 years ( 4 years). This study utilized the last six Shuttle flights, STS-128 to STS-134. The results show that partipating crewmembers experienced growth up to 6% in seated height and up to 3% in stature. Based on the worst case statistical analysis of the subject data, the recommended seated height growth of 6% will be provided to the designers as the necessary seated height adjustment.

Young, K. S.