Background Bone erosion in joint is the most deleterious effect induced by rheumatoid arthritis (RA) and is the major cause of disability. New therapies are urgently required to prevent RA-associated bone destruction. The excessive bone resorption in RA was proved to be mediated by osteoclasts which are derived from the monocyte/macrophage lineage and induced by RANKL. Therefore, RANKL could be a potential target for the preservation of bone mass in RA.
Objectives Chrysotherapy showed potential effects in reducing of joint destruction but with serious side-effects in RA therapy. A rational designed gold nanoparticle named GN was prepared to provide a choice for suppressing bone loss in RA therapy with more safety.
Methods Mice macrophage cell line RAW264.7 was activated by RANKL to evaluate the potential osteoclastogenesis suppressing effects of GN. The differentiation, fusion and function of osteoclast were assessed by tartrate-resistant acid (TRAP) staining, actin ring formation assay and osteologic discs detection respectively. Relative expressions of osteoclast-specific genes were evaluated by RT-PCR and the activity of NF-κB pathway as well as MAPK pathways were analyzed by immunoblotting.
Results Osteoclast differentiation, fusion and bone resorption were activated by RANKL in RAW264.7 cell, while GN significantly attenuates this process in a dose-dependent manner. The expressions of osteoclast-specific genes including TRAP and OSCAR were increased by RANKL stimulation but were effectively suppressed by GN. The activation of NF-kappa B pathway and MAPK pathways induced by RANKL was also suppressed by GN treatment.
Conclusions Our findings revealed that treatment with GN could prevent RANKL-induced osteoclastogenesis and reduce increased expression of osteoclast-specific genes which may through the suppression of NF-kB and MAPK activation in macrophage. GN may provide a basis for the design of chrysotherapy drugs that effect in progression of RA-associated articular erosions.
Disclosure of Interest None declared