SAT0330 Sclerostin concentrations in plasma and synovial fluid inversely correlate with disease severity in knee osteoarthritis
Authors: M.W. So, B.S. Koo, W.J. Seo, Y.-G. Kim, C.-K. Lee, B. Yoo
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Osteoarthritis (OA) is characterized by the progressive destruction of articular cartilage with joint space narrowing and osteophyte formation (1). Although the etiology and pathogenesis of OA remain poorly understood, recent studies have shown that biochemical factors with physiological factors play an important role in the development of OA. The Wnt-β-catenin signaling pathway has well-recognized roles as a critical regulator of bone and cartilage homeostasis (2). Previous many studies have suggested that elevated Wnt-β-catenin activity is a common mechanism in the excess bone formation and loss of overlying cartilage in OA (3). Sclerostin has been identified as an inhibitor of the Wnt pathways (4). <h3>Objectives</h3> We hypothesized that concentrations of sclerostin in plasma and synovial fluid might be associated with severity in knee OA patients. The aim of the present study was to evaluate the relationships between radiographic grading of knee osteoarthritis and plasma and synovial fluid concentrations of sclerostin. <h3>Methods</h3> Plasma and synovial fluid samples (n=87) were obtained from patients who underwent total knee replacement, arthroscopic partial meniscectomy, or arthroscopic cruciate ligament reconstruction. Disease severity was determined using radiographs of the knee and the Kellgren-Lawrence (K-L) grading scale. Sclerostin concentrations were evaluated using enzyme-linked immunosorbent assay. <h3>Results</h3> Radiographic OA patients (K-L grade ≥2) had lower sclerostin concentrations than controls (K-L grade 0 or 1) in both plasma (373.5±299.7 pg/ml vs. 1157.7±1097.3 pg/ml, p&lt;0.001) and synovial fluid (30.9±85.0 pg/ml vs. 434.6±641.0 pg/ml, p&lt;0.001). Sclerostin concentrations in synovial fluid were 3.5-fold lower than in corresponding plasma samples (193.3±454.3 pg/ml vs. 689.0±823.9 pg/ml, p&lt;0.001) and there was a positive correlation between plasma and synovial fluid sclerostin concentrations (r =0.904, p&lt;0.001). Sclerostin correlated negatively with knee OA severity for both plasma (r = -480, p&lt;0.001) and synovial fluid (r = -423, p&lt;0.001). <h3>Conclusions</h3> Sclerostin concentration in plasma and synovial fluid is inversely related to the severity of joint damage in knee OA. Sclerostin might play a role in the pathogenesis of the degenerative process of OA. <h3>References</h3> Felson DT, Zhang Y, Hannan MT, Naimark A, Weissman BN, Aliabadi P, et al. The incidence and natural history of knee osteoarthritis in the elderly. The Framingham Osteoarthritis Study. Arthritis Rheum 1995;38:1500-5. Blom AB, van Lent PL, van der Kraan PM, van den Berg WB. To seek shelter from the WNT in osteoarthritis? WNT-signaling as a target for osteoarthritis therapy. Curr Drug Targets 2010;11:620-9. Blom AB, Brockbank SM, van Lent PL, van Beuningen HM, Geurts J, Takahashi N, et al. Involvement of the Wnt signaling pathway in experimental and human osteoarthritis: prominent role of Wnt-induced signaling protein 1. Arthritis Rheum 2009;60:501-12. Lin C, Jiang X, Dai Z, Guo X, Weng T, Wang J, et al. Sclerostin mediates bone response to mechanical unloading through antagonizing Wnt/beta-catenin signaling. J Bone Miner Res 2009;24:1651-61. <h3>Disclosure of Interest</h3> None Declared