The microenvironment that cells reside in is a powerful regulator of both cell function and fate. Our goal is to understand the nature and influence of the cellular microenvironment. We know that both bone and cartilage are exquisitely sensitive to their mechanical environment and it is thought that the cells within bone and cartilage are the mechanosensors. We have developed systems for applying mechanical load to bone and cartilage cells in vitro, with which we can study effects of load on cell biology, for example, differentiation, cellular signaling, metabolism and gene expression. We are also examining the roles of potential candidate mechanosensors. Another critical regulator of bone cells is the oxygen availability. Under certain circumstances the oxygen levels around bone cells can decrease dramatically. For example cellular hypoxia occurs during bone unloading and at a fracture site due to disruption of the vasculature. Currently we are assessing the effects of hypoxia on bone cell differentiation and activity. We are looking at the influence of oxygen availability on stem cell migration and differentiation and their osteogenic capacity in 3D constructs for tissue engineering. In addition, we are assessing the potential of mesenchymal stem cells for bone, cartilage and tendon repair. Broadly the techniques we employ include fluorescence imaging, cell and molecular biology techniques and cellular electrophysiology. For more information, phone 530-754-6513, or e-mail cyellowley@ucdavis.edu.