GSH attenuates RANKL-induced osteoclast formation in vitro and LPS-induced bone loss in vivo

Abstract

Osteoclasts are capable of adhering the bone matrix, then secrete acid and lytic enzymes to resorb it. Reactive oxygen species (ROS), as a signaling messenger, plays an important role in the receptor activator nuclear factor κB ligand (RANKL) signal pathway during osteoclast differentiation. Glutathione (GSH) is known to be a powerful antioxidant which can scavenge intracellular ROS. This study aimed to investigate whether GSH can as a protective agent against the RANKL-stimulated osteoclastogenesis by suppressing intracellular ROS. Here, we showed that GSH markedly restricted RNAKL-induced differentiation of bone marrow-derived macrophages (BMMs) to form osteoclasts. GSH suppressed RANKL-induced ROS generation and subsequent ROS-induced NF-κB signaling pathways within BMMs during osteoclastogenesis. Further, GSH acted to significantly downregulate the osteoclastogenic genes expression of nuclear factor in activated T cells, cytoplasmic1 (NFATc1), C-fos, the tartrate-resistant acid phosphatase (TRAP), and osteoclast-associated immunoglobulin-like receptor (OSCAR). Our results suggested that GSH inhibits intracellular ROS-mediated NF-κB signal pathway involved in osteoclast differentiation. These findings might form the basis of a new strategy for treating bone disease associated with excessive bone resorption.

Keywords: Bone loss; Differentiation; Glutathione; Reactive oxygen species.