Psoriatic Arthritis is an inflammatory joint disease that can lead to chronic pain and disability. Joint destruction can be extensive and unique patterns of subchondral bone erosion have been noted but the mechanisms that underlie these changes are poorly understood. The overall goal of this project is for the Principal Investigator to develop the research skills necessary to become an independently funded investigator in patient-oriented research by studying osteoclast biology and bone resorption in the psoriatic joint under the mentorship of accomplished investigators in the field. In addition, protected time will allow the investigator to purse a Masters Degree in Public Health with a concentration in Clinical Investigation. These skills will be applied to defining the underlying mechanisms of bone resorption in psoriatic arthritis. Based on preliminary data from our laboratory, we hypothesize that: 1. Activated osteoclasts mediate focal bone resorption in the psoriatic joint. 2. Psoriatic synovial lining cells promote osteoclast differentiation and activation in adjacent bone through the expression of receptor activator of NFKB ligand (RANKL) which binds to its receptor RANK on the surface of osteoclasts and osteoclast precursors. 3. The circulating osteoclast precursor population is expanded in the peripheral blood of patients with PsA. 4. Treatment of PsA patients with the soluble TNF-p75 fusion protein (etanercept) will lessen joint inflammation and bone resorption through direct inhibition of TNF-a and down-regulation of TNF-mediated RANKL expression. To test these hypotheses we plan to perform studies with the following Specific Aims: 1. To demonstrate presence of osteoclasts at sites of bone resorption in PsA. 2. To define the expression pattern of TNF-a, RANK, RANKL and osteoprotegerin (OPG) in the psoriatic joint. 3. To determine if osteoclast precursors are expanded in the peripheral blood of patients with PsA. 4. To determine the effects of etanercept on inflammation, bone erosion, RANK and RANKL expression and circulating osteoclast precursor frequency as monitored by serial gadolinium enhanced MRI.
| Chiu, Yahui Grace; Ritchlin, Christopher T (2013) Characterization of DC-STAMP+ Cells in Human Bone Marrow. J Bone Marrow Res 1: |
| Chiu, Ya-Hui; Mensah, Kofi A; Schwarz, Edward M et al. (2012) Regulation of human osteoclast development by dendritic cell-specific transmembrane protein (DC-STAMP). J Bone Miner Res 27:79-92 |
| Chiu, Ya-Hui Grace; Ritchlin, Christopher T (2012) Biomarkers to Diagnose Early Arthritis in Patients With Psoriasis. Psoriasis Forum 18:2-10 |
