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Interstitial Fluid Flow in Bone Remodeling

The objective of this project is to develop and characterize in-vivo models of altered interstitial fluid flow (IFF) in bone, and to determine the role of IFF in bone remodeling. Our aims are to determine the remodeling patterns and significance of increased IFF in bone, and to develop an application based on altered IFF to prevent disuse osteopenia.

We will analyze the effect of increased venous pressure by femoral vein ligation in the rat by measuring femoral one dimensions, mechanical properties, mineral content, and mineral density.

The role of nitric oxide and prostaglandins in bone remodeling induced by venous ligation will be determined in murine models, utilizing NOS3-, and cyclooxygenase-knockout mice.

We will determine if temporary venous occlusion with an inflatable cuff leads to similar bone remodeling as seen with venous ligation.

The long-term goal is to determine the mechanisms of osteoporosis of disuse unduced by altered interstitial fluid flow. In addition, we will take a first step in the direction of a possible clinical application of our findings to develop a device to induce IFF-mediated bone remodeling.