Jacobs:Research:Loading Induced Fluid Flow and Disuse Bone Loss

Objective
Microgravity conditions result in a dramatic reduction of normal skeletal loading due to decreased weight bearing leading to rapid bone loss. A variety of countermeasures flown to date have not been effective in combating this bone loss. Interestingly, exposure to microgravity has been shown to result in decreased numbers of osteoblasts, but has little effect on osteoclasts. Cellular biophysical signals due to loading have been shown to regulate osteoblastic bone formation in vitro, however it is not known if such signals can regulate the formation of new osteoblasts. The population of osteoblasts is continually replenished by marrow stromal cells (MSCs), a population of multipotential cells that give rise to several mesenchymal phenotypes.

Our central hypothesis is that loading induced fluid flow may regulate the proliferation and differentiation of MSCs down the osteogenic pathway. In this three-year project we will examine the effect of loading-induced oscillatory fluid flow on MSCs in vitro.

Research Plan
This project is divided into three specific aims:


 * Determine the effect of loading-induced fluid flow on the mobilization of intracellular calcium and the mechanism whereby this occurs
 * Determine the effect of loading-induced fluid flow on proliferation and differentiation
 * Determine whether this effect involves intracellular calcium increase

Our results will be valuable both in terms of understanding the role of cellular physical signals in regulating osteoblast progenitor numbers and differentiation as well as identifying the mechanism of regulation leading to novel candidates for physical and pharmacological countermeasures.