期刊名称：Journal of Nutritional Science and Vitaminology
印刷版ISSN：0301-4800
电子版ISSN：1881-7742
出版年度：2017
卷号：63
期号：1
页码：28-34
DOI：10.3177/jnsv.63.28
出版社：Center for Academic Publications Japan
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) β, 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-κB ligand (RANKL) under normoglycemic (5.5 m M glucose), normoglycemic with high osmotic pressure (5.5 m M glucose + 10.0 m M mannitol), and hyperglycemic (15.5 m M 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 β by RANKL was significantly restored by high glucose, but not mannitol. Additionally, the deactivation of Lxrβ by siRNA attenuated high-glucose-induced suppression of osteoclastogenesis. Although further validation of the underlying pathway is necessary, targeting LXRβ is a potential therapeutic approach to treating osteoporosis.
关键词：osteoclast differentiation;hyperglycemia;liver X receptor β;LXRβ
