Ameliorative effects of follistatin-related protein/TSC-36/FSTL1 on joint inflammation in a mouse model of arthritis
✍ Scribed by Daisuke Kawabata; Masao Tanaka; Takao Fujii; Hisanori Umehara; Yoshimasa Fujita; Hajime Yoshifuji; Tsuneyo Mimori; Shoichi Ozaki
- Publisher
- John Wiley and Sons
- Year
- 2004
- Tongue
- English
- Weight
- 214 KB
- Volume
- 50
- Category
- Article
- ISSN
- 0004-3591
No coin nor oath required. For personal study only.
✦ Synopsis
Abstract
Objective
To clarify the in vivo function of follistatin‐related protein (FRP)/TSC‐36/FSTL1 in rheumatoid arthritis (RA), we investigated the roles of FRP in a mouse model of arthritis.
Methods
Arthritis was induced in BALB/c mice by injecting anti–type II collagen monoclonal antibody and lipopolysaccharide. Mice were treated with daily intraperitoneal injections of 20 μg of recombinant FRP. Development of arthritis was assessed by the clinical score and footpad swelling. Histologic examination of affected paws was performed on day 21 after the onset of arthritis. The gene expression profiles of affected paws in FRP‐treated and untreated mice were compared using commercially available complementary DNA (cDNA) arrays. The difference in gene expression was confirmed by real‐time quantitative reverse transcription–polymerase chain reaction.
Results
Treatment with recombinant FRP showed significant amelioration of the arthritis severity. Histologic analyses confirmed this finding and revealed the alleviation of cellular infiltration into the synovium as well as cartilage damage. The significant decrease in the amount of urinary deoxypyridinoline also indicated the ameliorative effect of FRP on joint destruction. Moreover, cDNA array analysis of the gene expression profile in FRP‐treated arthritic lesions revealed a reduced expression of the c‐fos, ets‐2, IL6, MMP3, and MMP9 genes, some of which are thought to be associated with synovial inflammation and joint destruction.
Conclusion
These findings from in vivo experiments suggest that FRP could be one of the key molecules in the treatment of inflammatory joint diseases such as RA.