Recipients of the Rheumatoid Arthritis Awards
Nicole Cherie Walsh, Ph.D.
Beth Israel Deaconess Medical Center, Boston
2006 Sontag Foundation Fellowship of the Arthritis National Research Foundation
Grant Award: $50,000
-- Dr. Nicole Cherie Walsh
About Dr. Walsh's Research:
The role of T cells in the pathogenesis of focal articular bone loss in inflammatory arthritis
The structural integrity of bone is maintained by the co-ordinated actions of two cell types, the bone-forming osteoblast and the bone-resorbing osteoclast. In the chronic inflammatory disease, Rheumatoid Arthritis (RA), there is an imbalance in the activities of these two cells, with osteoclast resorption activity predominating. This results in focal bone loss within the joints leading to joint deformity and pain. The exact mechanisms mediating this imbalance in bone formation and resorption activities have not been fully elucidated.
White blood cells such as T cells not only contribute to inflammation within the RA joint, but have also been implicated in mediating the formation of osteoclasts through the expression of receptor-activator of NF-kappaB ligand (RANKL), a membrane-bound protein that can be cleaved to produce an active soluble protein. There is also evidence to suggest that T cells may modulate osteoblast formation and function. Therefore, T cells represent a potential target for therapeutic intervention to prevent arthritis-induced bone loss.
Our experiments aim to test the hypothesis that T cells mediate focal bone loss in inflammatory arthritis through the regulation of both osteoclast and osteoblast differentiation. Studies completed during the first year of ANRF funding have determined that an immature population of osteoblast-osteoblast lineage cells persists at sites of focal bone erosion and that bone formation activity is altered at these sites. T cells were identified within the inflamed arthritic tissue, located near erosion sites. We have preliminary evidence in vitro that suggests that activated T cells express factors that are known inhibitors of osteoblast differentiation and function.
In this second year of funding, we will focus on defining the role of T cells in modulating osteoblast differentiation and function at sites of arthritis-induced focal bone erosion. We will determine if T cells, in the setting of inflammatory arthritis, produce factors that impair osteoblast differentiation and function and identify the mechanisms by which these factors function. A clearer understanding of the mechanisms regulating osteoblast differentiation and function in RA, and the role T cells play in this, will allow the identification of targets for promoting bone formation at these sites, a necessary step in restoring joint function in RA.
