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

Abstract

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.

Anti-Osteoporotic and Anti-Adipogenic Effects of the Water Extract of Drynaria roosii Nakaike in Ovariectomized Mice Fed a High-Fat Diet

“…The profile of phytochemicals identified in WDR coincides with that in previous reports [10,38,39,40]. The anti-osteoporotic effects of coumarin (esculetin), flavonoids (naringin, eriodictyol, naringenin, and kaempferide), and phenolics (protocatechuic acid and chlorogenic acid) have been reported in in vitro and in vivo studies [41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57]. These phytochemicals inhibited RANKL-induced osteoclastogenesis and osteoclastic bone resorption in vitro and suppressed lipopolysaccharide or ovariectomy-induced bone loss in vivo.…”

Pregnenolone Inhibits Osteoclast Differentiation and Protects Against Lipopolysaccharide-Induced Inflammatory Bone Destruction and Ovariectomy-Induced Bone Loss

“…Similarly, the MAPK signaling triad of ERK, p38 and JNK are activated by phosphorylation which enables nuclear translocation and binding to respective DNA response elements to cooperatively activate transcription of target genes. Genetic deletion or pharmacological inhibition these signaling cascades have been shown to arrest osteoclast formation and bone resorption (Karakawa et al, 2009;Kameda et al, 2013;Mediero et al, 2013;Ma et al, 2015;Jiao et al, 2017;Kim et al, 2018). The efficient early activation NF-kB and MAPK is necessary for the downstream induction and upregulation of transcription factors c-Fos and NFATc1.…”

Bone-targeted PAMAM micelle to treat bone metastases of lung cancer

“…After that, gold palladium was sprayed on the cranium to observe bone lacunae on cranium tissue by SEM. For observing osteoclasts, the cranium was stained with Trap and methyl green, then the osteoclasts on cranium tissue was observed by using microscope [34,35].…”