Kaempferide Prevents Titanium Particle Induced Osteolysis by Suppressing JNK Activation during Osteoclast Formation

Kaempferide (KF) is an O-methylated flavonol, a natural plant extract, which is often found in Kaempferia galanga. It has a variety of effects including anti-carcinogenic, anti-inflammatory, anti-oxidant, anti-bacterial and anti-viral properties. In this study, we aimed to investigate whether KF effectively inhibits titanium particle induced calvarial bone loss via down regulation of the JNK signaling pathway. In the mice with titanium particle induced calvarial osteolysis, the Low dose of KF mildly reduced the resorption pits while in the high dose group, fewer scattered pits were observed on the surface of calvarium. Histological examination showed fewer osteoclasts formation in the KF group. In mouse bone marrow macrophages (BMMs) and RAW264.7 cells, KF significantly inhibited the osteoclast formation and bone resorption at 12.5 μM. However, KF does not affect the mature osteoclast F-actin ring formation. But when being co-treated with KF and anisomycin, BMMs differentiated into mature osteoclasts. At the molecular levels, the JNK phosphorylation was inhibited and the osteoclastogenesis-related specific gene expression including V-ATPase d2, TRAP, calcitonin receptor (CTR), c-Fos and NFATc1 was markedly suppressed. In conclusion, these results indicated that KF is a promising agent in the treatment of osteoclast-related diseases.