Hypothalamic regulation of bone
- 1Neuroscience Program, Garvan Institute of Medical Research, St Vincent's Hospital, Sydney 2010, New South Wales, Australia
2Faculty of Medicine, University of New South Wales, Sydney 2052, New South Wales, Australia
- (Correspondence should be addressed to P A Baldock who is now at Bone and Mineral Research Program, Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, Sydney, New South Wales 2010, Australia; Email: p.baldock{at}garvan.org.au)
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Figure 1
Model of leptin and serotonin signaling in the regulation of bone and fat formation. Leptin modulates bone mass through receptors (ObRb) in the brainstem, which stimulate serotonergic neurons. Subsequent serotonin binding to HTR2C receptors on VMH neurons alters bone mass, and HTR1A and 2B receptors on ARC neurons alter appetite. The activity of ObRb in these nuclei is an open question.
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Figure 2
Model of neuromedin U signaling in the regulation of bone formation. As a central regulator of a leptin-dependent regulation of bone mass, neuromedin U acts in the central nervous system downstream of leptin. Efferent sympathetic signaling through the sympathetic nervous system (SNS) affects the molecular clock in bone to regulate bone remodeling.
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Figure 3
Model of CART signaling in the regulation of bone remodeling. CART expression is altered in proportion to serum leptin levels. Low CART expression induces an increase in bone resorption through higher levels of RANKL, while increased hypothalamic CART expression produces a higher bone mass phenotype.
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Figure 4
Model of NPY signaling for the regulation of bone formation. Neuropeptide Y signals in the hypothalamus via Y2 receptors inhibit the function of osteoblasts. Y1 receptors expressed on osteoblasts also inhibit osteoblast activity. The local role of osteoblastic NPY, which is inhibited by mechanical loading, is yet to be determined.
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Figure 5
Model of cannabinoids signaling for the regulation of bone formation. The cannabinoid receptor 1 (CB1) is distributed in brain areas associated with motor control, energy, and bone homeostasis and in the periphery in osteoblasts. The CB2 receptor is mainly expressed in the peripheral tissues like osteoclasts but also osteoblasts and osteocytes. The contribution of central vs peripheral CB1 and CB2 receptors in mediating the effect of cannabinoids on bone remains to be determined.
- © 2010 Society for Endocrinology
