Dr. Oursler is leading several ongoing research projects in the Cell Biology of Bone Laboratory. These research projects include:
- Osteoclast stimulation of osteoblast recruitment and differentiation
- Osteoclasts as a source of Wnt proteins in the bone microenvironment
- Anti-adhesive mucine PODXL role in osteoclast formation and activity
- Balance of canonical and noncanonical Wnt signaling control of bone metabolism and alteration in aging
Osteoclast stimulation of osteoblast recruitment and differentiation
The Cell Biology of Bone Lab uses both in vivo and in vitro approaches to determine the molecular mechanisms by which osteoclasts recruit osteoblasts and stimulate bone formation during the reversal phase subsequent to bone resorption.
Dr. Oursler's research team has discovered that osteoclasts secrete bone morphogenetic protein-6, Wnt10b and the chemokine sphingosine-1-phosphate to promote bone formation. The lab is examining the roles of each of these coupling factors and how they're regulated during osteoclast differentiation.
Because bone formation lags behind bone resorption during aging, Dr. Oursler's team is examining the impact of aging on osteoclast coupling factor production. Researchers have found that osteoclast-mediated release of bone-bound transforming growth factor-beta is a crucial stimulator of coupling in mice. The Cell Biology of Bone Lab is pursuing the molecular mechanisms of this process and extending these coupling observations to humans.
Current anti-resorptive therapies reduce osteoblast-mediated bone formation, most likely because of osteoclast suppression. Understanding how osteoclasts promote bone formation may lead to new therapies to suppress osteoclast resorption activity while preserving anabolic osteoclast functions.
Osteoclasts as a source of Wnt proteins in the bone microenvironment
Wnt (Wingless-related integration site) proteins are a family of secreted factors that are necessary for differentiation of osteoblasts. Dr. Oursler's lab has published research findings showing that osteoclasts express several Wnt proteins.
In order to evaluate the role of osteoclast Wnt production in bone metabolism, the research team has reduced expression of Wls, an intracellular protein required for Wnt processing and secretion, in osteoclasts. This process causes osteopenia by reducing bone formation and elevating osteoclast numbers.
The lab is also evaluating the role of osteoclast Wnt production in coupling of bone resorption to subsequent bone formation.
Anti-adhesive mucine PODXL role in osteoclast formation and activity
PODXL is a heavily glycosylated and charged membrane protein that acts to repel cells. The Cell Biology of Bone Lab has found that PODXL membrane expression must be downregulated for osteoclast precursor fusion. In mature cells, a low level of expression is required for osteoclasts to resorb bone.
The lab is also studying the impact of the loss of PODXL on bone metabolism in vivo, the mechanisms by which it is downregulated during osteoclast differentiation, and how it functions to promote bone resorption.
Balance of canonical and noncanonical Wnt signaling control of bone metabolism and alteration in aging
The Cell Biology of Bone Lab has discovered that the relative expression levels of canonical and noncanonical Wnt receptors in osteoclast precursors determine whether Wnt signaling suppresses or stimulates osteoclast differentiation.
Dr. Oursler's research team is also investigating the mechanisms of Wnt control of differentiation and how the balance is altered with aging.