Prussian blue nanoparticles prevent RANKL-induced osteoclastogenesis by scavenging ROS and inactivating NF-κB/MAPK signaling pathways

The accumulation of intracellular reactive oxygen species (ROS) is widely recognized to stimulate the development of osteoclasts, a crucial factor in the onset of osteoporosis. The ROS scavenging capability of Prussian blue nanoparticles (PBNPs) is exceptional, and they possess excellent biocompatibility. However, the effects of PBNPs on osteoporosis remain unknown. Present study aimed to investigate whether PBNPs could inhibit osteoclast differentiation and prevent ovariectomy (OVX)-induced bone loss by suppressing ROS. In vitro experiments demonstrated that PBNPs attenuated osteoclastogenesis and downregulated the expression of osteoclast-related genes. Mechanistically, PBNPs reduce cellular ROS by blocking RANKL-induced ROS generation and increasing the expression of ROS scavenging enzymes, which in turn block the NF-κB, ERK, JNK, and p38 pathways, thereby reducing NFATc1 signaling. According to in vivo experimental results, OVX caused a significant rise in ROS in the bone marrow, an increase in osteoclastic number on the bone surface, and substantial bone loss; however, PBNPs significantly reduced ROS and successfully protected OVX-induced bone damages. In conclusion, this study showed for the first time that PBNPs prevented OVX-induced bone loss and attenuate osteoclastogenesis, indicating that PBNPs may be a viable alternative therapy for the management of osteoclast-associated bone disorders. Graphical Once RANKL binds to RANK on the cell membrane of BMMs, the NF-κB and MAPK pathways become activated, resulting in the amplification of NFATc1, which upregulates the expression of osteoclast-specific genes such as CTSK , Integrin αV , Atp6v0d2 , and MMP9 . These signaling events are mediated by the RANKL-induced ROS signaling. PBNPs decreased levels of ROS and mitigated these signaling pathways by decreasing ROS production and enhancing the expression of antioxidant enzymes. Consequently, PBNPs prevented osteoclastogenesis.