Evaluation of Osteoclastogenesis via NFκB Decoy/mannosylated Cationic Liposome-Mediated Inhibition of Pro-inflammatory Cytokine Production from Primary Cultured Macrophages

Abstract

To explore the effect of NFκB activation in macrophages on osteoclastogenesis of bone marrow cells for potential application as a new type of therapy for preventing bone loss. Primary cultured macrophages and bone marrow cells were prepared from mice. As macrophage-targeted carriers, Mannosylated cationic liposomes (Man-liposomes) were prepared and were allowed to form complexes with NFκB decoy (a double-stranded oligonucleotide). Cellular uptake, inhibition of NFκB activation, and cytokine production were evaluated using macrophages. Osteoclastogenesis was investigated using bone marrow cells, which were cultured in the conditioned medium prepared from macrophages with or without Man-liposome/NFκB decoy complexes treatment. Cellular accumulation of NFκB decoy was enhanced by Man-liposome. NFκB activation in macrophages and TNF-α production were suppressed in macrophages by Man-liposome/NFκB decoy complexes but not by the naked NFκB decoy, Gal-liposome/NFκB decoy complexes, or Man-liposome/random decoy complexes. Osteoclastogenesis of bone marrow cells was induced in the conditioned medium prepared from activated macrophages but not by activated macrophages treated with Man-liposome/NFκB decoy complexes. Osteoclastogenesis induced by activated macrophages could be suppressed by the treatment macrophages with Man-liposome/NFκB decoy complexes. Macrophage-targeted delivery of NFκB decoys using Man-liposomes may be promising in its use for the remediation of bone loss.