Fluvastatin Inhibits Osteoclast Differentiation and P. gingivalis lipopolysaccharide-Induced Alveolar Bone Erosion in Mice.

Statins have been widely used to treat hypercholesterolemia. In addition to the inhibition of cholesterol synthesis, recent reports suggest bone anabolic property of statins. However, little notice has been paid to the direct effect of statins on osteoclastogenesis and bone resorption.,The effect of fluvastatin on osteoclast differentiation was determined using in vitro culture of mouse bone marrow macrophages (BMMs) in the presence of macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor kappa B ligand (RANKL). The role of fluvastatin on bone erosion was examined in the P. gingivalis lipopolysaccharide (LPS)-induced alveolar bone loss model in mice.,Fluvastatin significantly inhibited both RANKL- and LPS-induced osteoclast differentiation in mouse BMMs. Fluvastatin also markedly reduced the expression of osteoclast differentiation marker genes of Acp5, Calcr, and Ctsk as well as fusion markers, Atp6v0d2 and Dcstamp. These were accompanied by the decreased expression of c-Fos and NFATc1 transcription factors. Fluvastatin reduced the generation of reactive oxygen species (ROS) upon the addition of RANKL and LPS, suggesting an anti-oxidant role. Finally, the administration of fluvastatin in mice conspicuously reduced P. gingivalis LPS-induced osteoclastogenesis and alveolar bone erosion in vivo.,Combined, these results suggest that fluvastatin directly inhibited osteoclastogenesis and efficiently blocked bone erosion.