Bone loss and increased osteoclastogenesis

Bone loss being a type I risk in microgravity and here on earth with osteoporosis and ageing, should be given paramount focus. One of the best documented pathophysiological changes associated with exposure to microgravity is bone loss; bone mineral densit y (BMD) has been shown to decrease at a rate of approximately 1-2% per month during long duration space flight. Reduction in BMD (2-4% per year) also happens to be a major unsolved problem in disease states such as osteoporosis and rheumatoid arthritis. Bones are important systems involved in locomotion and the maintenance of posture in the 1xg terrestrial environment. Osteoclasts have been implicated as key mediators of all forms of bone loss in rheumatoid arthritis and osteoporosis. Orthopedic implan t loosening is also accelerated by osteoclastic bone resorption resulting from the action of cytokines produced in response to phagocytosis of implant derived wear particles. The increased bone resorption is attributed to an inflammatory response linked to the activation of the immune system and its production of a number of cytokines/signaling molecules. The major goals of this project are the adaptation and characterization of bone resorption models at the cellular level that can be utilized to mechani stically develop countermeasures that may have use at the organismal level. This study will establish an in vitro model of osteoclast/osteoblast culture in which a number of potential countermeasures to increased osteoclast activation/bone resorption can be tested in a mechanistic fashion. Studies will be performed using the NASA rotating wall vessel (RWV) bioreactor as a ground-based culture analog of microgravity conditions, including co-culture of osteoclasts and osteoblasts, to greater mimic the cel lular interactions found in vivo.