Macrophage migration inhibitory factor is essential for osteoclastogenic mechanisms in vitro and in vivo mouse model of arthritis

Macrophage migration inhibitory factor (MIF) enhances activation of leukocytes, endothelial cells and fibroblast-like synoviocytes (FLS), thereby contributing to the pathogenesis of rheumatoid arthritis (RA). A MIF promoter polymorphism in RA patients resulted in higher serum MIF concentration and worsens bone erosion; controversially current literature reported an inhibitory role of MIF in osteoclast formation. The controversial suggested that the prease role of MIF and its putative receptor CD74 in osteoclastogenesis and RA bone erosion, mediated by locally formed osteoclasts in response to receptor activator of NF-kappa B ligand (RANKL), is unclear. We reported that in an in vivo K/BxN serum transfer arthritis, reduced clinical and histological arthritis in MIF-/- and CD74(-/-) mice were accompanied by a virtual absence of osteoclasts at the synovium-bone interface and reduced osteoclast-related gene expression. Furthermore, in vitro osteoclast formation and osteoclast-related gene expression were significantly reduced in MIF-/- cells via decreasing RANKL-induced phosphorylation of NF-kappa B-p65 and ERK1/2. This was supported by a similar reduction of osteoclastogenesis observed in CD74(-/-) cells. Furthermore, a MIF blockade reduced RANKL-induced osteoclastogeriesis via deregulating RANKL-mediated NF-kappa B and NFATc1 transcription factor activation. These data indicate that MIF and CD74 facilitate RANKL-induced osteoclastogenesis, and suggest that MIF contributes directly to bone erosion, as well as inflammation, in RA. (C) 2014 Elsevier Ltd. All rights reserved

Electrochemical Biosensors for miRNA Detection

MicroRNAs (miRNAs) are intensely studied as candidates for diagnostic and prognostic biomarkers. They are naturally occurring small RNAs (approximately 22 nucleotides in length) that act as regulators of protein translation. Because many diseases are caused by the misregulated activity of proteins, miRNAs have been implicated in a number of diseases including a broad range of cancers, heart disease, and immunological and neurological diseases. A great deal of effort, therefore, has been devoted to developing analytical methods for miRNA analysis. The consideration when selecting existing or designing new methods for miRNA analysis includes sensitivity and multiplexing capability without PCR. In this chapter, novel electrochemical strategies for miRNA detection and quantification will be reviewed