Follistatin-like protein 1: a serum biochemical marker reflecting the severity of joint damage in patients with osteoarthritis

Arthritis Res Ther. 2011;13(6):R193. doi: 10.1186/ar3522. Epub 2011 Nov 25.


Introduction: Follistatin-like protein 1 (FSTL1) is a secreted glycoprotein that has been implicated in arthritis pathogenesis in a mouse model. The aim of this study is to detect FSTL1 expression and to further assess its potential utility as a biomarker of joint damage in osteoarthritis (OA) patients.

Methods: FSTL1 expression was detected by real-time PCR, western blot and immunohistochemistry (IHC) in the synovial tissues (STs) and by IHC in the articular cartilage from OA patients and control trauma patients. The serum and synovial fluid (SF) FSTL1 concentrations were measured by ELISA in OA patients and control individuals. Linear regression analyses were used to assess correlations between the serum FSTL1 levels and the clinical characteristics in OA patients.

Results: The FSTL1 mRNA and protein levels were substantially elevated in the STs from OA patients compared with those from control trauma patients. The FSTL1 expression was strong in the cytoplasm of the synovial and capillary endothelial cells of the STs, but weak in the chondrocytes of the articular cartilage from OA patients. Furthermore, the serum and SF FSTL1 concentrations were significantly higher in OA patients than in respective control subjects. Interestingly, the serum and SF FSTL1 levels were markedly higher in female OA patients than in males. Importantly, bivariate regression analysis revealed that the serum FSTL1 levels in female OA patients had significant correlations with Kellgren and Lawrence (KL) grade, joint space narrowing (JSN) and the Western Ontario McMaster and Universities Osteoarthritis (WOMAC) stiffness subscale, an inverse correlation with height, and marginal correlations with the total WOMAC score and the WOMAC function subscale. Multivariate regression analysis revealed that the serum FSTL1 levels correlated independently with KL grade in female OA patients. Bivariate analysis also revealed that the serum FSTL1 levels correlated significantly with age and disease duration, and they correlated marginally with high sensitivity C-reactive protein (hs-CRP) and KL grade in male OA patients.

Conclusions: Increased FSTL1 expression may be a characteristic of OA patients. FSTL1 is a potential serum biomarker that may reflect the severity of joint damage, and further studies are required to evaluate its potential application for monitoring the course of the disease and the efficacy of therapies in OA patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biomarkers / blood*
  • Blotting, Western
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Follistatin-Related Proteins / blood*
  • Follistatin-Related Proteins / genetics
  • Follistatin-Related Proteins / metabolism
  • Humans
  • Immunohistochemistry
  • Knee Joint / metabolism*
  • Knee Joint / pathology
  • Linear Models
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Osteoarthritis, Knee / blood*
  • Osteoarthritis, Knee / pathology
  • Reverse Transcriptase Polymerase Chain Reaction
  • Severity of Illness Index
  • Sex Factors
  • Synovial Fluid / metabolism
  • Synovial Membrane / metabolism
  • Synovial Membrane / pathology


  • Biomarkers
  • Follistatin-Related Proteins