anisomycin and Osteolysis

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.

Topics: Animals; Anisomycin; Cell Differentiation; Cells, Cultured; Gene Expression Regulation; Immunohistochemistry; JNK Mitogen-Activated Protein Kinases; Kaempferols; MAP Kinase Signaling System; Mice; Models, Molecular; Molecular Conformation; Osteoclasts; Osteogenesis; Osteolysis; Protective Agents; RANK Ligand; Structure-Activity Relationship; Titanium; X-Ray Microtomography

The aim of this study was to assess the effect of naringenin on osteoclastogenesis and titanium particle-induced osteolysis. Osteolysis from wear-induced particles and aseptic loosening are the most frequent late complications of total joint arthroplasty leading to revision of the prosthesis. Osteolysis during aseptic loosening is most likely due to increased bone resorption by osteoclasts. Through in vitro studies, we demonstrated that naringenin, a naturally occurring flavanone in grapefruit and tomatoes, exerts potent inhibitory effects on the ligand of the receptor activator of nuclear factor-κB (RANKL)-induced osteoclastogenesis and revealed that the mechanism of action of naringenin, which inhibited osteoclastogenesis by suppression of the p38 signaling pathway. Through in vivo studies, we proved that naringenin attenuated titanium particle-induced osteolysis in a mouse calvarial model. In general, we demonstrated that naringenin inhibited osteoclastogenesis via suppression of p38 signaling in vitro and attenuated titanium particle-induced osteolysis in vivo. This study also suggested that naringenin has significant potential for the treatment of osteolysis-related diseases caused by excessive osteoclast formation and activity.

Topics: Actins; Animals; Anisomycin; Bone Resorption; Cell Death; Cell Differentiation; Extracellular Signal-Regulated MAP Kinases; Flavanones; Gene Expression Regulation; Humans; JNK Mitogen-Activated Protein Kinases; MAP Kinase Signaling System; Mice, Inbred C57BL; Models, Biological; NF-kappa B; NFATC Transcription Factors; Osteoclasts; Osteogenesis; Osteolysis; p38 Mitogen-Activated Protein Kinases; RANK Ligand; Titanium