AB0072 Rational designed gold nanoparticle suppresses rankl-induced osteoclastogenesis in raw264.7 cells via NF-KAPPA B pathway and MAPK pathways

Q Yuan, X Gao
2017 Abstracts Accepted for Publication   unpublished
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
more » ... 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 tartrateresistant 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 RANKLinduced osteoclastogenesis and reduce increased expression of osteoclastspecific 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.
doi:10.1136/annrheumdis-2017-eular.2087 fatcat:ezrk5msocrcbxhzwm3fdtvhgka