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1. Effects of Simulated Microgravity on Human Osteoblast Behavior: A Proteomics Study

Microgravity during space flight can cause many physiological changes including cephalic fluid shift, bone and muscle loss, negative calcium balance, cardiovascular alterations, and reduced immune response. Of these, bone loss or osteopenia may have severe consequences, especially for prolonged space travel (astronauts lose up to 2 percent of their bone mass per month in space). The countermeasures to prevent bone loss in the absence of microgravity, such as physical exercise, do not help in space. In order to develop effective countermeasures to prevent spaceflight-associated pathologies, there is a critical need to understand the mechanisms of how microgravity affect cell behavior and functionality. Although studies have shown alterations in cell morphology, gene expression, and protein expression of osteoblasts and osteocytes in response to microgravity and mechanical stimuli, a systematic investigation of microgravity-induced alterations in protein expression is necessary to unfold the mechanisms. To this end, we have examined the protein expression of human osteoblasts under simulated microgravity conditions using a comparative proteomics approach. Both 2-D gel-based and mass spectrometry based analysis were employed..

We found that microgravity alters the expressions of many types of proteins in human osteoblasts. Many of these proteins are known to affect osteoblast function, such as differentiation, proliferation, and maturation. A proteomics approach is a powerful tool to identify the differences in protein expressions by cells under different environmental conditions. In addition, microgravity bioreactors and dynamic compression/tension force bioreactors allow long-term investigation of human cell/tissue behavior and function under microgravity.

Figure. 1: 2-D gel

Figure. 2: SEM pictures show the morphology differences between static group and microgravity group. Immunostaining show the differences in osteocalcin expression (red color) between two groups.

2. Proteomics of brain astrocytes

Immature astrocytes, but not mature astrocytes, have been shown to suppress glial scar formation, reduce inflammation, and hasten the restoration of blood-brain barrier (BBB) following CNS injury by physical contact with host tissue. Such effect of immature astrocytes is mediated, at least in part, via a soluble factor releasing mechanism [Read the full Paper]. These data suggest the potential utility of immature astrocytes derived soluble factors as functionalizing reagents in the design of implants for spinal cord repair. However, the exact soluble factors that suppressing the scar formation is unknown. The goal of this project is to identify this potent factor using state of the art techniques in proteomics and genomics. Then we will combine the identified factor into the therapeutic strategy for glial scar-free spinal cord repair.