Strategies of Manipulating BMP Signaling in Microgravity to Prevent Bone Loss.

Bone structure and function is shaped by gravity. Prolonged exposure to microgravity leads to 1-2% bone loss per month in crew members compared to 1% bone loss per year in postmenopausal women. Exercise countermeasures developed to date are ineffective in combating bone loss in microgravity. The search is on for alternate therapies to prevent bone loss in space. Microgravity is an ideal stimulus to understand bone interactions at different levels of organizations. Spaceflight experiments are limited by high costs and lack of opportunity. Ground-based microgravity analogs have proven to simulate biological responses in space. Mice experiments have given important signaling clues in microgravity-associated bone loss, but are restricted by numbers and human application. Cell-based systems provide initial clues to signaling changes; however, the information is simplistic and limited to the cell type. There is a need to integrate information at different levels and provide a complete picture which will help develop a unique strategy to prevent bone weakening. Limited exposure to simulated microgravity using random positioning machine induces proliferation and differentiation of bipotential murine oval liver stem cells. Bone morphogenetic proteins (BMPs) are the prototypal osteogenic signaling molecule with multitude of bone protective functions. In this chapter, we discuss the basic BMP structure, its significance in bone repair, and stem cell differentiation in microgravity. Based on the current information, we propose a model for BMP signaling in space. Development of new technologies may help osteoporosis patients, bedridden people, spinal injuries, or paralytic patients.