Most bone-related diseases are characterized by excessive bone resorption by osteoclasts. Receptor activator of nuclear factor-kappa B (NF-κB) ligand (RANKL) has emerged as a major mediator of bone resorption, commonly associated with cancer and chronic inflammatory diseases. Thus inhibitors of RANKL signaling have a potential in preventing bone loss. In the present study, we investigated the ability of triptolide, a diterpenoid isolated from Thunder of God Vine, to inhibit signaling by receptor activator of NF-κB (RANK) and its ligand (RANKL) and to modulate osteoclastogenesis induced by RANKL and human cancer cells. We found that triptolide suppressed RANKL-induced differentiation of precursor cells to osteoclasts, and also inhibited osteoclast formation induced by human breast tumor cells (MDA-MB-231), multiple myeloma cells (U266) and prostate tumor cells (PC-3). Triptolide inhibited RANKL-induced NF-κB activation in osteoclast precursor cells by inhibiting IκBα kinase activation, IκBα phosphorylation, and IκBα degradation. Our results suggest that triptolide effectively inhibits RANKL-induced NF-κB activation and RANKL- and tumor cell-induced osteoclastogenesis. This warrants further study of triptolide as a potential therapy for osteoporosis and cancer-associated bone loss.
Keywords: Bone resorption; NF-κB; Osteoclastogenesis; RANKL; Triptolide.
Copyright © 2014 Elsevier Masson SAS. All rights reserved.