Molecular Mechanisms of the Inhibitory Effects of Bovine Lactoferrin on Lipopolysaccharide-mediated Osteoclastogenesis

摘要: Lactoferrin (LF) is an important modulator of the immune response and inflammation. It has also been implicated in regulation bone tissue. In our previous study we demonstrated that bovine LF (bLF) reduces LPS-induced resorption through a reduction TNF-α production vivo. However, it was not known how bLF inhibits LPS-mediated RANKL (receptor activator nuclear factor κB ligand) osteoblasts. this show impairs production. inhibited osteoclastogenesis via osteoblasts co-culture system. Furthermore, pretreatment NFκB DNA binding activity as well IκBα IKKβ (IκB kinase β) phosphorylation. MAP activation by pretreatment. failed to block degradation IRAK1 (interleukin-1 receptor-associated 1), which essential event after its activation. Remarkably, found Lys-63-linked polyubiquitination TNF 6 (TRAF6). We mainly endocytosed LRP1 (lipoprotein receptor-related protein-1) intracellular distributed binds endogenous TRAF6. addition, IL-1β- flagellin-induced TRAF6-dependent signaling pathway. Collectively, findings demonstrate activation, play critical roles chronic inflammatory disease interfering with TRAF6 process. Thus, could be potent therapeutic agent for diseases associated destruction, such periodontitis rheumatoid arthritis.