Follistatin-like protein 1 is a mesenchyme-derived inflammatory protein and may represent a biomarker for systemic-onset juvenile rheumatoid arthritis.

Abstract

OBJECTIVE:

To examine both the source of follistatin-like protein 1 (FSTL-1) and the factors that induce its expression in arthritis, and to determine whether juvenile rheumatoid arthritis (JRA) is characterized by overexpression of FSTL-1.

METHODS:

FSTL-1 expression patterns were analyzed by immunohistochemical staining of joint tissue derived from mice with collagen-induced arthritis. Induction of FSTL-1 secretion was assessed in osteoblasts, adipocytes, and human fibroblast-like synoviocytes in response to transforming growth factor beta (TGFbeta), interleukin-1beta (IL-1beta), tumor necrosis factor alpha (TNFalpha), and IL-6. In addition, sera and synovial fluid from children with oligoarticular, polyarticular, or systemic-onset JRA were assayed for FSTL-1 using a custom enzyme-linked immunosorbent assay. FSTL-1 concentrations in these patients were assessed for correlations with the erythrocyte sedimentation rate (ESR) and platelet count.

RESULTS:

Immunohistochemical staining of murine joint sections demonstrated expression of FSTL-1 in all cell types of the mesenchymal lineage, including osteocytes, chondrocytes, adipocytes, and fibroblasts. FSTL-1 could be induced in osteoblasts, adipocytes, and human fibroblast-like synoviocytes by TGFbeta, IL-1beta, TNFalpha, and IL-6. The IL-1beta response was significantly greater than the TNFalpha response (P < 0.05). In human serum and synovial fluid, only those samples from children with the systemic-onset JRA subtype had elevated concentrations of FSTL-1. The synovial fluid concentrations of FSTL-1 were 2-3-fold higher than the serum concentrations. The elevation in serum FSTL-1 concentrations seen in children with systemic-onset JRA correlated closely with elevations in the ESR and platelet count.

CONCLUSION:

These findings demonstrate that the arthritic joint matrix is a major source of FSTL-1 and that IL-1beta is a central mediator of FSTL-1 secretion. Furthermore, FSTL-1 may represent a useful biomarker of disease activity in systemic-onset JRA.

• Authors: David C Wilson, Anthony D Marinov, Harry C Blair, Daniel S Bushnell, Susan D Thompson, Yury Chaly, Raphael Hirsch
• Journal: Arthritis and rheumatism (Arthritis Rheum) Vol. 62 Issue 8 Pg. 2510-6 (Aug 2010) ISSN: 1529-0131 [Electronic] United States
• PMID: 20506332 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers
• Cytokines
• Follistatin-Related Proteins
• Fstl1 protein, mouse

Topics

• Adolescent
• Animals
• Arthritis, Experimental (metabolism)
• Arthritis, Juvenile (metabolism)
• Biomarkers (metabolism)
• Cells, Cultured
• Child
• Chondrocytes (drug effects, metabolism)
• Cytokines (metabolism, pharmacology)
• Female
• Follistatin-Related Proteins (metabolism)
• Humans
• Immunohistochemistry
• Joints (drug effects, metabolism)
• Male
• Mice
• Mice, Inbred DBA
• Osteoblasts (drug effects, metabolism)
• Synovial Fluid (drug effects, metabolism)
• Synovial Membrane (drug effects, metabolism)
• Young Adult