HEALTH NEWS

Study Title:

Lactoferrin Slows Down Osteoclasts

Study Abstract

Lactoferrin (LF) is an important modulator of the immune response and inflammation. It has also been implicated in the regulation of bone tissue. In our previous study, we demonstrated that bovine LF (bLF) reduces LPS-induced bone resorption through a reduction of TNF-αproduction by osteoblasts. However, it was not known how bLF inhibits LPS-mediated TNF-α and RANKL production in osteoblasts. In the present study, we show that bLF impairs LPS-mediated TNF-α and RANKL (Receptor activator of nuclear factor kappa-B ligand) prodiction. bLF inhibited LPS-mediated osteoclastogenesis via osteoblasts in a co-culture system. Furthermore, bLF pretreatment inhibited LPS-induced NFκB DNA binding activity, as well as IκBα and IKKβ phosphorylation. MAP kinase activation was also inhibited by bLF pretreatment. However, bLF pretreatment failed to block the degradation of IRAK1 (iterleukin-1 receptor-associated kinase 1), which is an essential event following its activation. Remarkably, we found that bLF pretreatment inhibited LPS-mediated K63-linked polyubiquitination of TNF receptor-associated factor 6 (TRAF6). We also found that endocytosed bLF bound to endogenous TRAF6. In addition, bLF inhibited IL-1β and Flagellin induced TRAF6-dependent activation of the NFκB signaling pathway. Collectively, our findings demonstrate that bLF inhibits NFκB and MAP kinase activation, which play critical roles in chronic inflammatory disease, by interfering with the TRAF6 polyubiquitination process. Thus, bLF could be a potent therapeutic agent for inflammatory diseases associated with bone destruction, such as periodontitis and rheumatoid arthritis.

Study Information

Inubushi T, Kawazoe A, Miyauchi M, Kudo Y, Ao M, Ishikado A, Makino T, Takata T
Molecular mechanisms of the inhibitory effects of bovine Lactoferrin on LPS-mediated osteoclastogenesis.
J Biol Chem.
2012 May
Hiroshima University Graduate School of Biomedical Sciences, Japan.