title: Hyperglycemia Suppresses RANKL-Induced Osteoclast Differentiation through LXRβ Expression in RAW264.7 Cells.
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.
authors.affiliation: Division of Vascular Surgery, Department of Surgery, University of Wisconsin School of Medicine and Public Health.
authors.forename: Teruyoshi
authors.initials: T
authors.lastname: Tanaka
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Takei
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Zaima
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Moriyama
authors.forename: Dai
authors.initials: D
authors.lastname: Yamanouchi
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D015870:Gene Expression / Q000187:drug effects; D005947:Glucose / Q000494:pharmacology; D006943:Hyperglycemia; D000071518:Liver X Receptors / Q000037:antagonists & inhibitors / Q000235:genetics*; D008264:Macrophages / Q000166:cytology / Q000187:drug effects; D051379:Mice; D010010:Osteoclasts / Q000166:cytology*; D010012:Osteogenesis / Q000187:drug effects; D053245:RANK Ligand / Q000502:physiology*; D000067996:RAW 264.7 Cells; D012333:RNA, Messenger / Q000032:analysis; D034741:RNA, Small Interfering / Q000494:pharmacology
chemical_list: D000071518:Liver X Receptors; D053245:RANK Ligand; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D005947:Glucose