Age-related bone loss and the coincident increase in skeletal fracture risk are caused in part by decreased bone formation relative to resorption. Matrix-bound osteocytes, regulated by physical and biochemical stimuli, are key mediators of bone-forming osteoblasts. While current 2D monoculture models have enriched our knowledge of bone cell biology, they cannot address interactions between osteocytes, osteoblasts, and the 3D extracellular mineral-collagen environment. There is a critical need to develop 3D co-culture systems that mimic native bone tissue architecture and composition to identify the key physical and biochemical factors regulating bone cells in their natural environment. 

The short-term goal of this work is to develop a novel 3D co-culture system that reproduces in vivo osteocyte-osteoblast interactions and their responses to osteocyte-directed fluid flow to determine the biological consequences of fluid shear stress on bone anabolic processes in a realistic 3D cellular environment. Future applications of this 3D co-culture system will accelerate translational research by examining the mechanistic role of cellular transcription factors in osteocyte-regulated anabolic pathways and serve as a pre-clinical testbed for determining the efficacy of physical and pharmacologic therapies for treating pathologic bone loss.