Dickkopf-1 induces migration in fibroblast-like synoviocytes

Rheumatoid arthritis (RA) is a chronic autoimmune disease affecting joint tissues. Disease is characterized by synovial hyperproliferation and joint invasion, severe inflammatory cell influx and matrix destruction. Serum levels of the wnt antagonist, Dickkopf-1, are increased in diseased patients and have been described to affect bone homeostasis in affected joints. Here we introduce an additional role for Dickkopf-1, the induction of migration in fibroblast-like synoviocytes (FLS) in vitro. Our results show that Wnt5a and surprisingly, DKK1 induce migration in wound edge C57Bl/6 FLS. Wnt5a has previously been demonstrated to induce migration in a JNK dependent manner whereas DKK1 has been implicated in both induction and inhibition of migratory behavior. Migrating FLS exhibit activation of JNK1 and JNK2, and the absence of either isoform limits the induction of synoviocyte migration, indicating that JNK is required for FLS migration. However, Dickkopf-1 treatment of JNK1 deficient FLS was able to induce migration in wound edge cells, while JNK2 deficient FLS were refractory. These findings suggest that the Wnt signaling pathways contribute to migration in FLS in vitro. Elevated signaling through Wnt- affiliated molecules may account for the aberrant migratory behavior of synovial cells in rheumatoid arthritis patient

The emerging role of biomarkers and bio-impedance in evaluating hydration status in patients with acute heart failure.

The quantitative and qualitative estimation of total body fl uid content has proven to be crucial for both diagnosis and prognosis assessment in patients with heart failure. The aim of this review is to summarize the current techniques for assessing body hydration status as well as the principal biomarkers associated with acute heart failure (AHF). Although clinical history, physical examination and classical imaging techniques (e.g., standard radiography and echocardiography) still represent the cornerstones, novel and promising tools, such as biomarkers and bio-electrical impedance are achieving an emerging role in clinical practice for the assessment of total body fluid content. In the acute setting, the leading advantages of these innovative methods over device are representedby the much lower invasiveness and the reasonable costs, coupled with an easier and faster application. This article is mainly focused on AHF patients, not only because the overall prevalence of this disease is dramatically increasing worldwide, but also because it is well-known that their fluid overload has a remarkable diagnostic and prognostic significance. It is thereby conceivable that the bio-electrical vector analysis (BIVA) coupled with laboratory biomarkers might achieve much success in AHF patient management in the future, especially for assisting diagnosis, risk stratifi cation, and therapeutic decision-making