Departments of Medicine, Pediatrics & Pharmacology, Division of Endocrinology & Metabolism
- Mechanical control of bone remodeling
- Mesenchymal stem cell differentiation: Osteoblast/Adipocyte
The skeleton is a complex tissue that is able to regulate its own mass and architecture to meet two critical and competing responsibilities: one structural and the other metabolic. The structure of bone is determined largely through its ability to respond to daily loading with intelligent remodeling. When mechanical signals are suppressed (no exercise, space travel, getting old) bone structure degenerates - and bone resorption outpaces bone formation. If skeletal degeneration is severe it will lead to catastrophic failure with fracture. Alternatively, daily skeletal loading leads to bone formation, enhancing not only the activity of bone osteoblasts to make new bone, but also promotes the entry of mesenchymal stem cells into the osteogenic lineage. Our cellular and molecular biological investigations are aimed at understanding mechanical and hormonal control of bone remodeling.
Our current primary focus is to understand the role of biophysical forces experienced by the skeleton during exercise, in controlling bone remodeling. We are interested in signaling events that enhance osteoblast activity - in particular the ability of mechanical factors to activate MAPK, beta-catenin and NFATc1. These signals appear to have regulatory roles not only in promoting bone formation and inhibiting bone resorption, but also in preventing mesenchymal stem cell entry into the adipocyte lineage. Other signals which appear to have important roles in promoting bone function and repressing fat function include COX2, nitric oxide, IGF-1 and vitamin D. Eventually we hope to be able to apply this understanding to improving bone structure by using non-pharmacologic strategies.