TY - JOUR
T1 - Hyperglycemia suppresses RANKL-induced osteoclast differentiation through LXRβ expression in RAW264.7 cells
AU - Tanaka, Teruyoshi
AU - Takei, Yuichiro
AU - Zaima, Nobuhiro
AU - Moriyama, Tatsuya
AU - Yamanouchi, Dai
N1 - Publisher Copyright:
© 2017, Center for Academic Publications Japan. All rights reserved.
PY - 2017
Y1 - 2017
N2 - 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 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 Lxrβ 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.
AB - 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 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 Lxrβ 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.
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U2 - 10.3177/jnsv.63.28
DO - 10.3177/jnsv.63.28
M3 - Article
C2 - 28367923
AN - SCOPUS:85016284752
SN - 0301-4800
VL - 63
SP - 28
EP - 34
JO - Journal of Nutritional Science and Vitaminology
JF - Journal of Nutritional Science and Vitaminology
IS - 1
ER -