Neuropeptide FF (NPFF) has been implicated in many physiological processes. Previously, we have
reported that NPFF modulates the viability and nitric oxide (NO) production of RAW264.7 macrophages. In
this study, we investigated the influence of NPFF on lipopolysaccharide (LPS)-mediated osteoclast formation
of RAW264.7 cells. Our results suggest that, NPFF dose-dependently (1 nM, 10 nM and 100 nM) inhibited
osteoclast formation, TRAP enzyme activity and bone resorption in osteoclasts induced by LPS respectively.
Moreover, LPS-provoked NO release was also inhibited by NPFF treatment, indicating a NO-dependent pathway is
mainly involved. Furthermore, the alterations of osteoclast marker genes were also assessed including TRAP, Cathepsin
K, MMP-9, NFATc1 and Runx2. NPFF downregulated LPS-caused gene augmentations of TRAP, Cathepsin K and
MMP-9, whereas showed no influences on NFATc1 and Runx2. In addition, NPFF receptor 2 (NPFFR2) mRNA expression
was also augmented in response to NPFF treatment, hinting the involvement of NPFFR2 pathway. It should be mentioned
that RF9 (1 µ M), a reported pharmacological inhibitor for NPFF receptors, exerted NPFF-like agonist properties
as to attenuate osteoclastogenesis. Collectively, our findings provide new evidence for the in vitro activity of NPFF on osteoclasts,
which may be helpful to extend the scope of NPFF functions.