The Role of Osteoclasts in Controlling Bone-Forming Osteoblasts
During normal development, osteoclast-mediated bone degradation and osteoblast-mediated bone formation is tightly coupled. Much is known about how osteoblasts control osteoclasts, but little is known about how osteoclasts control osteoblasts. Recently, it has become apparent that active osteoblasts require the presence of osteoclasts and we are determining what is produced by osteoclasts that stimulate osteoblast differentiation and activity. The communication between osteoclasts and osteoblasts breaks down in the aging skeleton. We are studying the contribution of changes in osteoclast secreted proteins in this break down.
The Mechanisms of Wnt Signaling Influences Osteoclast Differentiation
Global loss of Wnt signaling is devastating for bone formation and there is great interest in improving Wnt signaling as a therapeutic target to promote bone formation. We have made the novel observation that osteoclasts produce Wnts and Wnt signaling decreases bone resorption by suppressing osteoclast differentiation. This project focuses on resolving the mechanisms by which Wnts control osteoclast differentiation.
Regulation Of Osteoclast Precursor Fusion
We are examining a membrane mucine that has anti-adhesive properties in tumor cells. We found that this protein is highly expressed in osteoclast precursors and expression and membrane localization rapidly decreases during differentiation. Selective deletion of this gene in early osteoclast lineage cells enhances precursor fusion. We are examining the roles of this protein in bone metabolism and how it is regulated during osteoclast differentiation.