Osteoclasts are multinucleated cells of hematopoietic origin that are responsible for the degradation of old bone matrix. Osteoclast differentiation and activity are controlled by two essential cytokines, macrophage colony-stimulating factor (M-CSF) and the receptor activator of nuclear factor-κB ligand (RANKL). M-CSF and RANKL bind to their respective receptors c-Fms and RANK to stimulate oste...

Pathological bone loss always reflects enhanced net osteoclastic activity. Recognition and binding of the receptor activator of NF-κB (RANK) by RANK ligand (RANKL) is the key osteoclastogenic event, and the signaling cascades induced by this reaction therefore contain potential anti-osteoporosis therapeutic targets. A study reported in this issue of the JCI documents that a pivotal component of...

The range of applications for aptamers, small oligonucleotide-based receptors binding to their targets with high specificity and affinity, has been steadily expanding. Our understanding the mechanisms governing aptamer-ligand recognition is however lagging, stymieing progress in rational design new aptamers optimization known ones. Here we demonstrate capabilities limitations native ion mobilit...

Lead optimization benefits from including structural knowledge of the target. We present a new method that exploits quantitatively NMR amide proton chemical shift perturbations (CSP) on the protein side for protein-ligand docking. The approach is based on a hybrid scoring scheme consisting of a weighted sum of DrugScore, describing protein-ligand interactions, and Kendall's rank correlation coe...

Giant cell tumor (GCT) of the bone also known as osteoclastoma typically arises from meta-epiphyseal region long and comprises 5% all tumors 20% benign tumors. Understanding pathogenesis is key to successful systemic therapy with denosumab, a RANK-ligand inhibitor. In this context, we report seven GCT bone-treated denosumab radiotherapy cases diverse clinical presentation our institute, NRS Med...

Signaling by receptor activator of nuclear factor κB (RANK) in response to its ligand RANKL, which is a member of the tumor necrosis factor (TNF) superfamily of cytokines, stimulates osteoclast formation and bone resorption. Thus, this ligand-receptor pair is a therapeutic target for various disorders, such as osteoporosis and metastasis of cancer to bone. RANKL exists as a physiological homotr...

The implementation of a novel sequential computational approach that can be used effectively for virtual screening and identification of prospective ligands that bind to trypanothione reductase (TryR) is reported. The multistep strategy combines a ligand-based virtual screening for building an enriched library of small molecules with a docking protocol (AutoDock, X-Score) for screening against ...