Volume 21 Issue 3, March 2015

Osteoclasts are required for bone resorption. A new study in mice indicates that osteoclast differentiation is stabilized by DNA methylation at Irf8 (encoding interferon regulatory factor 8) mediated by DNA methyltransferase 3a (Dnmt3a), which suppresses Irf8 gene expression. The activity of Dnmt3 in osteoclasts requires elevated oxidative metabolism.

The NLRP3 inflammasome is involved in the molecular etiology of multiple autoinflammatory diseases. Two studies identify inhibitors of NLRP3 activation and might pave the way for new treatment options for a variety of diseases.

Experimental modeling of cancer typically uses in vitro culture of transformed cell lines or in vivo animal models. A new study using CRISPR-Cas9 to engineer oncogenic mutations into three-dimensional human colon organoid cultures yields insights into colorectal cancer tumorigenesis.

New methods for detecting indications of neurodegeneration are necessary to diagnose neurodegenerative diseases. In identifying suitable biomarkers that can be monitored by these techniques, the pathogenic mechanisms that lead to these diseases may also be elucidated.

Tau pathology is commonly analyzed by positron emission tomography (PET) imaging. However, recently developed cell-based techniques for analyzing tau pathogenicity may also be used to measure an early biomarker in tauopathies.

The progress in understanding the mechanistic causes of anemias such as hemoglobinopathies and rare genetic disorders, as well as advances in therapies for anemias are reviewed.

Ovarian tumors with common mutations in the epigenetic regulator ARID1A are shown to be sensitive to inhibition of EZH2, another epigenetic regulator, showing a synthetic lethality that could potentially be exploited therapeutically

Genetic and pharmacological inhibition of the high-affinity LTB4 receptor promotes improved metabolism in obese mice.

A selective, small-molecule inhibitor of NLRP3 suppresses activation of the inflammasome in vitro and in vivo and attenuates inflammatory disease.

Genome editing applied to human intestinal organoids enables the study of the functional effects of mutations recurrent in human tumors.

Ketone bodies are elevated in response to fasting, a low-carbohydrate ketogenic diet or high-intensity exercise. Vishwa Deep Dixit and colleagues report that one metabolite, β-hydroxybutyrate, inhibits the NLRP3 inflammasome. In vivo, β-hydroxybutyrate is anti-inflammatory and suppresses NLRP3-mediated inflammatory disease.

Use of a new generation anti-sense oligonucleotide to target exon skipping in multiple organ systems in two mouse models of muscular dystrophy

Inhibition of Hsp90 as its C-terminus allows for the mature folding of GR and its full activity, thus ameliorating Cushing symptoms in a mouse model.

Proper bone structure is dependent on metabolism-mediated epigenetic regulation of osteoclast development.