Glycosphingolipids (GSLs) are essential constituents of cell membranes and lipid rafts and can modulate signal transduction events. The contribution of GSLs in osteoclast (OC) activation and osteolytic bone diseases in malignancies such as the plasma cell dyscrasia multiple myeloma (MM) is not known. Here, we tested the hypothesis that pathological activation of OCs in MM requires de novo GSL synthesis and is further enhanced by myeloma cell–derived GSLs. Glucosylceramide synthase (GCS) inhibitors, including the clinically approved agent
Adel Ersek, Ke Xu, Aristotelis Antonopoulos, Terry D. Butters, Ana Espirito Santo, Youridies Vattakuzhi, Lynn M. Williams, Katerina Goudevenou, Lynett Danks, Andrew Freidin, Emmanouil Spanoudakis, Simon Parry, Maria Papaioannou, Evdoxia Hatjiharissi, Aristeidis Chaidos, Dominic S. Alonzi, Gabriele Twigg, Ming Hu, Raymond A. Dwek, Stuart M. Haslam, Irene Roberts, Anne Dell, Amin Rahemtulla, Nicole J. Horwood, Anastasios Karadimitris
GSL inhibitors inhibit osteoclastogenesis and bone resorption in vitro.