682. Over-Expression of Follistatin-Like Protein Exacerbates Collagen Induced Arthritis

Abstract

Follistatin-like protein (FSTL-1) is a secreted glycoprotein with a molecular weight of 40-55 KD that contains a follistatin-like domain. FSTL-1 was first isolated from a cDNA library of mouse osteoblastic cells as a transforming growth factor-|[beta]|1-inducible gene. Its function has not yet been fully elucidated. We found increased expression of FSTL-1 mRNA by microarray analysis of joints of mice with collagen-induced arthritis (CIA). In situ hybridization and immunohistochemistry revealed increased expression along the margin of contact between the inflammatory synovium and eroding bone. The highest level of FSTL-1 expression was seen during the acute phase of CIA. To further investigate the role of FSTL-1 in arthritis, non-replicating adenoviral vectors encoding either the human or mouse FSTL-1 gene were administered intravenously to mice one week before the onset of arthritis. Both human and mouse FSTL-1 exacerbated arthritis. Mice receiving either vector developed earlier and more severe arthritis, compared to mice administered a control virus. Liver homogenates from mice administered FSTL-1 adenoviral vectors had increased IL-1|[beta]| levels. These results suggest that FSTL-1 is a pro-inflammatory molecule that might serve as a novel target for therapy of arthritis.