Monosodium glutamate-sensitive hypothalamic neurons contribute to the control of bone mass.
Using chemical lesioning we previously identified hypothalamic neurons that are required for leptin antiosteogenic function. In the course of these studies we observed that destruction of neurons sensitive to monosodium glutamate (MSG) in arcuate nuclei did not affect bone mass. However MSG treatment leads to hypogonadism, a condition inducing bone loss. Therefore the normal bone mass of MSG-treated mice suggested that MSG-sensitive neurons may be implicated in the control of bone mass. To test this hypothesis we assessed bone resorption and bone formation parameters in MSG-treated mice. We show here that MSG-treated mice display the expected increase in bone resorption and that their normal bone mass is due to a concomitant increase in bone formation. Correction of MSG-induced hypogonadism by physiological doses of estradiol corrected the abnormal bone resorptive activity in MSG-treated mice and uncovered their high bone mass phenotype. Because neuropeptide Y (NPY) is highly expressed in MSG-sensitive neurons we tested whether NPY regulates bone formation. Surprisingly, NPY-deficient mice had a normal bone mass. This study reveals that distinct populations of hypothalamic neurons are involved in the control of bone mass and demonstrates that MSG-sensitive neurons control bone formation in a leptin-independent manner. It also indicates that NPY deficiency does not affect bone mass.
Elefteriou
Florent
F
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA.
Takeda
Shu
S
Liu
Xiuyun
X
Armstrong
Dawna
D
Karsenty
Gerard
G
D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000166:cytology* / Q000502:physiology; D001862:Bone Resorption / Q000503:physiopathology; D005260:Female; D007006:Hypogonadism / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009478:Neuropeptide Y / Q000235:genetics*; D010012:Osteogenesis / Q000502:physiology*; D012970:Sodium Glutamate / Q000494:pharmacology*
D009478:Neuropeptide Y; D012970:Sodium Glutamate