Hyperglycemia Suppresses RANKL-Induced Osteoclast Differentiation through LXR beta Expression in RAW264.7 Cells

卷:63

Tanaka, Teruyoshi ; Takei, Yuichiro ; Zaima, Nobuhiro ; Moriyama, Tatsuya ; Yamanouchi, Dai

Univ Wisconsin

关键词: osteoclast differentiation;    hyperglycemia;    liver X receptor beta;    LXR beta;   

DOI  :  

学科分类：食品科学和技术

【 摘 要 】

There have been reports that hyperglycemia suppresses osteoclast (OCL) differentiation, although the underlying mechanism is poorly understood. Here we demonstrated that high glucose suppresses OCL differentiation through activation of liver X receptor (LXR) beta, a recently reported glucose-sensing nuclear receptor. The effect of hyperglycemia on osteoclastogenesis was tested in RAW264.7 cells, a murine macrophage cell line. Cells were treated with receptor activator of NF-kappa B ligand (RANKL) under normoglycemic (5.5 mM glucose), normoglycemic with high osmotic pressure (5.5 mM glucose + 10.0 mM mannitol), and hyperglycemic (15.5 mM glucose) conditions. RANKL-induced osteoclastogenesis was significantly suppressed by high-glucose treatment. Mannitol treatment also significantly suppressed osteoclastogenesis, but the inhibitory effect was lower than for high-glucose treatment. The suppression of mRNA expression of Lxr beta by RANKL was significantly restored by high glucose, but not mannitol. Additionally, the deactivation of Lxr beta by siRNA attenuated high-glucose-induced suppression of osteoclastogenesis. Although further validation of the underlying pathway is necessary, targeting LXR beta is a potential therapeutic approach to treating osteoporosis.