Hyperglycemia Suppresses RANKL-Induced Osteoclast Differentiation through LXRß Expression in RAW264.7 Cells.
J Nutr Sci Vitaminol (Tokyo)
; 63(1): 28-34, 2017.
Article
en En
| MEDLINE
| ID: mdl-28367923
ABSTRACT
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) ß, 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 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 Lxrß by RANKL was significantly restored by high glucose, but not mannitol. Additionally, the deactivation of Lxrß by siRNA attenuated high-glucose-induced suppression of osteoclastogenesis. Although further validation of the underlying pathway is necessary, targeting LXRß is a potential therapeutic approach to treating osteoporosis.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Osteoclastos
/
Diferenciación Celular
/
Ligando RANK
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Receptores X del Hígado
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Hiperglucemia
Límite:
Animals
Idioma:
En
Revista:
J Nutr Sci Vitaminol (Tokyo)
Año:
2017
Tipo del documento:
Article