Functional Characterization of the Receptor Activator of NF-.KAPPA.B(RANK) Extracellular Domain.

Abstract

Receptor activator of NF-kB (RANK) and its ligand, receptor activator of NF-kB ligand (RANKL) play a crucial role in the differentiation and activation of osteoclasts. In order to evaluate the efficacy of RANK, we designed a soluble murine RANK (sRANK) and compared its functional activitywith Osteoprotegerin (OPG), a soluble decoy receptor for RANKL. sRANK was expressed in baculovirus-infected Sf-9 cells and purified by Ni-NTA chromatography followed by MonoQ column elution. The binding affinity of the purified sRANK to RANKL was quite similar to that of OPG. Furthermore, the inhibitory effect on RANKL-induced osteoclastogenesis from mouse bone marrow cells showed no significant difference between sRANK and OPG. However, sRANK had no effect on TNF-related apoptosisinducing ligand (TRAIL) -induced apoptosis, although OPG prevented the cytotoxic activity of TRAIL. The results of this study suggest that recombinant sRANK may have therapeutic value as an inhibitor of bone resorption.