title: 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.
  
  
  CONCLUSIONS
  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.affiliation: Children's Hospital of Pittsburgh of University of Pittsburgh Medical Center and University of Pittsburgh, Pittsburgh, Pennsylvania 15224, USA.
authors.forename: David C
authors.initials: DC
authors.lastname: Wilson
authors.forename: Anthony D
authors.initials: AD
authors.lastname: Marinov
authors.forename: Harry C
authors.initials: HC
authors.lastname: Blair
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Bushnell
authors.forename: Susan D
authors.initials: SD
authors.lastname: Thompson
authors.forename: Yury
authors.initials: Y
authors.lastname: Chaly
authors.forename: Raphael
authors.initials: R
authors.lastname: Hirsch
mesh_terms: D000293:Adolescent; D000818:Animals; D001169:Arthritis, Experimental / Q000378:metabolism*; D001171:Arthritis, Juvenile / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D002478:Cells, Cultured; D002648:Child; D019902:Chondrocytes / Q000187:drug effects / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism / Q000494:pharmacology; D005260:Female; D038702:Follistatin-Related Proteins / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D007596:Joints / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism*; D013582:Synovial Fluid / Q000187:drug effects / Q000378:metabolism*; D013583:Synovial Membrane / Q000187:drug effects / Q000378:metabolism; D055815:Young Adult
chemical_list: D015415:Biomarkers; D016207:Cytokines; D038702:Follistatin-Related Proteins; C448720:Fstl1 protein, mouse