Hyperglycemia suppresses RANKL-induced osteoclast differentiation through LXRβ expression in RAW264.7 cells

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

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)

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) 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.

Original languageEnglish
Pages (from-to)28-34
Number of pages7
JournalJournal of Nutritional Science and Vitaminology
Volume63
Issue number1
DOIs
Publication statusPublished - 2017
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Medicine (miscellaneous)
  • Nutrition and Dietetics

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