Aim 1: examine the response of wild-type and CX43-deficient (via crispr gene editing) murine osteocytes (OCY454) to simulated microgravity in vitro using a high aspect ratio vessel (harv). Aim 2:…

This is a $300,000.00 federal grant awarded by the National Aeronautics and Space Administration (NASA) to Virginia Commonwealth University (VCU) to examine the effects of simulated microgravity on bone cells and bone health.

The grant, which runs from July 2018 to December 2023, has two main goals: 1) to study the response of normal and genetically modified (CRISPR-edited) mouse bone cells to simulated microgravity conditions in vitro using a specialized bioreactor, and 2) to examine the impact of simulated microgravity on bones from genetically modified mice that lack a specific protein (Cx43) in their bone cells.

This research aims to provide new insights into the mechanisms underlying bone loss under microgravity conditions, which is critical for supporting astronaut health during spaceflight. The award does not utilize any set-aside designations. VCU is the prime recipient of this grant, drawing upon its expertise and infrastructure in biomedical research related to bone biology and microgravity effects.

Aim 1: examine the response of wild-type and CX43-deficient (via crispr gene editing) murine osteocytes (OCY454) to simulated microgravity in vitro using a high aspect ratio vessel (harv). Aim 2: examine the effect of simulated microgravity in vivo on bones from osteocyte-specific CX43-deficient mice. CX43 will be selectively deleted from mice using a CRE recombinase approach similar to what we previously used to delete CX43 from osteoblasts and osteocytes. Using well-established experimental paradigms like the harv apparatus and HLS greatly increases the probability of successfully completing our aims and attaining important, novel findings. Collectively, our infrastructure and expertise, in combination with multiple unique reagents, place US in an unparalleled position to rapidly and significantly advance knowledge pertaining to the mechanisms underlying microgravity-induced bone loss. These aims and the experiments designed therein represent a substantive departure from our current understanding and will reveal novel targets for countermeasures.