Y2 and Y4 receptor signalling attenuates the skeletal response of central NPY.

Journal of Molecular Neuroscience : MN
N J LeeP A Baldock

Abstract

Both the neuropeptide Y (NPY) and the leptin systems have been shown to be important central mediators of bone metabolism. However, the interaction between these two systems is complex and not fully understood. Here, we show that a unique interaction exists between Y2 and Y4 receptors in the regulation of bone homeostasis that is not evident when combined with lack of Y1 signalling. Despite the hypoleptinaemia shown in male Y2/Y4 double knockout (Y2⁻/⁻ Y4⁻/⁻) mice, when on the leptin-deficient ob/ob background, these mice display reduced cancellous bone mass. However, combined Y2/Y4 deletion enhances the effect of leptin deficiency on the cortical bone compartment. By replicating the enhanced central NPY expression evident in ob/ob mice using virally mediated overexpression of NPY in the hypothalamus of Y receptor knockout mice, we demonstrate that Y2⁻/⁻ Y4⁻/⁻ mice have an exaggerated response to the anti-osteogenic effects of elevated hypothalamic NPY in both cancellous and cortical bone and that this effect appears to be dependent on Y1 receptor signalling. This study highlights the complex interaction between Y receptors in the control of bone mass. Moreover, it suggests that the reduction in cortical bone observed in the ab...Continue Reading

References

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Mar 5, 2010·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Nicola J LeeHerbert Herzog

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Citations

Oct 11, 2015·Bone·Peter HouwelingPaul A Baldock
Oct 10, 2012·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Iris P L WongPaul A Baldock
Nov 9, 2017·Toxicologic Pathology·Alexander CorrPaul Baldock
Jan 12, 2019·Journal of Neuroendocrinology·Nicola J LeeHerbert Herzog
Mar 2, 2012·Scientific Reports·Konstantin KlemmMaxi San Miguel

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