Abstract
IntroductionFollistatin-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.MethodsFSTL1 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.ResultsThe 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.ConclusionsIncreased 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.
Highlights
Follistatin-like protein 1 (FSTL1) is a secreted glycoprotein that has been implicated in arthritis pathogenesis in a mouse model
Consistent with our previous report [9], the FSTL1 mRNA levels were upregulated in the synovial tissue (ST) of rheumatoid arthritis (RA) patients by approximately 1.71-fold compared with the controls
We found that the FSTL1 mRNA levels in OA patients were elevated by approximately 1.49-fold and 2.55-fold compared with RA patients and the controls, respectively (Figure 1A)
Summary
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. The progressive deterioration of joint structure and function has prompted studies to identify potential biomarkers of the damage to articular cartilage and subchondral bone as well as markers to monitor the progression of the disease and facilitate the design of proper treatment [3,4]. Further studies demonstrate that FSTL1 has potential preventive effects on joint destruction by inhibiting the production of matrix metalloproteinases (MMPs) and cytokines both in synovial cells in vitro and in mouse models in vivo [11,12]. Conflicting data have shown that FSTL1 is a new proinflammation mediator that causes and aggravates arthritis by promoting the expression of IL-1b, TNFa and IL-6 and by enhancing the IFNg signaling pathways in a mouse model [8,15]
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