The lack of disease-modifying treatments for osteoarthritis (OA) is linked to a shortage of suitable biomarkers. This study combines multi-molecule synovial fluid analysis with machine learning to produce an accurate diagnostic biomarker model for end-stage knee OA (esOA). Synovial fluid (SF) from patients with esOA, non-OA knee injury, and inflammatory knee arthritis were analyzed for 35 potential markers using immunoassays. Partial least square discriminant analysis (PLS-DA) was used to derive a biomarker model for cohort classification. The ability of the biomarker model to diagnose esOA was validated by identical wide-spectrum SF analysis of a test cohort of ten patients with esOA.Aims
Methods
Tendon healing begins with inflammation and results in an incomplete repair with fibrosis, culminating in tendon pathology along with tissue degeneration. Inflammatory mediators regulate the expression of growth factors, and members of the TGFβ superfamily including BMPs have been suggested to play a key role in the development of fibrosis. In established tendon diseases where inflammation and reparative processes persists, the cellular phenotype of tendon cells has been implied to undergo a transformation from that of normal tissue. This study investigates the inflammation-driven mechanisms of tendon pathology using an Diseased human tendon cells were isolated from patients with large to massive rotator cuff tears (n=4). Cells isolated from healthy human hamstring tendons served as control tissue (n=5). Cells were treated with human recombinant IL-1β (5ng/ml), oncostatin M (10ng/ml), IL-6 (10ng/ml), IL-10 (10ng/ml) in serum-free medium, or serum-free medium alone (control) for 24 hours. Cell viability was monitored by Alamar Blue assay, and expression of Introduction
Materials and Methods
Dickkopf-3 is upregulated in OA cartilage and synovial tissue. In vitro studies show Dkk3 can prevent cartilage degradation and antagonise Wnt signaling. We hypothesis that Dkk3 can protect against OA-related cartilage destruction. Our group has previously shown that Dkk3, a member of the Dkk family of Wnt antagonists, is upregulated in OA cartilage and synovium. Levels of Dkk3 in synovial fluid are also increased in individuals with tricompartmental OA and after arthroscopy. The role of Dkk3 in cartilage or the factors regulating its expression are not currently understood. Correct regulation of cell signalling pathways is integral to cartilage homeostasis and thus the prevention of OA pathogenesis. Dkk3 is a member of the Dkk family of Wnt antagonists and therefore may impact on chondrocyte biology through interaction with the Wnt pathway. Dkk3 has also been found to influence TGFβ signalling in other cell systems.Summary Statement
Introduction
This paper outlines the recent development of an exchange Travelling Fellowship scheme between the British and American Orthopaedic Research Societies.