Decreased physical activity can cause bone loss in many conditions, including long-term bed rest, weightlessness, and paralysis. The manifestations of this bone loss have been quantified primarily by assessing bone mass at a macroscale, above the level of the osteocyte, the most abundant bone cell. Osteocytes form an interconnected network throughout bone tissue, and when bone is mechanically loaded during physical activity, fluid in the small pores surrounding osteocytes is forced to flow. This load-induced fluid flow is believed to play a role in bone's biological response by translating whole body forces to the cellular. Recent studies demonstrate that the osteocyte can actively alter its local bone architecture. The research goal of this project is to investigate whether reduced mechanical loading causes the bone cells to alter the bone porosities and environment, such that bone's ability to detect mechanical loading is diminished. Such a disruption could be an important contributing factor to the overall degradation of bone strength in reduced loading conditions. Results from this work will make a significant contribution to understanding how reduced mechanical loading affects bone strength and may enable the development of targeted clinical approaches that eliminate the bone loss that occurs in disuse osteoporosis. In addition to supporting graduate students in the research, high school students will also be involved and new teaching modules will be created and incorporated into undergraduate classes.
This work will assess bone microstructural and cellular-level changes due to a mechanical challenge of decreased loading. A rat disuse osteoporosis model will be used to investigate the effect of reduced mechanical loading on osteocyte-level parameters temporally using high-resolution microscopy. A non-invasive mechanical loading device will then be utilized to assess functional changes in interstitial fluid movement using injected tracers to quantify the effective osteocyte pericellular matrix pore size. High-resolution micro-CT analyses will also be performed to assess bone microarchitectural changes due to disuse, including vascular porosity changes. Then the microstructural measurements will be input into poroelastic models to calculate cellular-level strains for disuse and controls. The application of mechanical loading to counteract bone loss from disuse will also be evaluated to test whether tissue structure can be restored if osteocytes experience their usual mechanical input. By investigating the influence of in vivo mechanical forces on cell and matrix biology in the maintenance of bone tissue, this high-resolution experimental and computational study will yield important details about bone mechanotransduction.
