A Novel Role for RILP in Regulating Osteoclastogenesis and Bone Resorption

Abstract

Increased bone resorption caused by excessive number or activity of osteoclasts is the main cause of osteoporosis. Osteoclasts are multinucleated cells that are formed by the fusion of precursor cells. Although osteoclasts are primarily characterized by bone resorption, our understanding of the mechanisms that regulate the formation and function of osteoclasts is poor. Here we showed that the expression level of Rab interacting lysosomal protein (RILP) was strongly induced by receptor activator of NF-κB ligand in mouse bone marrow macrophages. Inhibition of RILP expression induced a drastic decrease in the number, size, F-actin ring formation of osteoclasts, and the expression level of osteoclast-related genes. Functionally, inhibition of RILP reduced the migration of preosteoclasts through PI3K-Akt signaling and suppressed bone resorption by inhibiting the secretion of lysosome cathepsin K. Treatments with siRNA-RILP attenuated pathologic bone loss in disease models induced by lipopolysaccharide. Thus, this work indicates that RILP plays an important role in the formation and bone resorption function of osteoclasts and may have a therapeutic potential to treat bone diseases caused by excessive or hyperactive osteoclasts.