Genetic determination of the cellular basis of the ghrelin-dependent bone remodeling

Molecular Metabolism
Chengshan MaShu Takeda

Abstract

Bone mass is maintained through a balance of bone formation and resorption. This homeostatic balance is regulated by various systems involving humoral and local factors. The discovery that the anorexigenic hormone leptin regulates bone mass via neuronal pathways revealed that neurons and neuropeptides are intimately involved in bone homeostasis. Ghrelin is a stomach-derived orexigenic hormone that counteracts leptin's action. However, the physiological role of ghrelin in bone homeostasis remains unknown. In this study, through the global knockout of ghrelin receptor (Ghsr) followed by tissue-specific re-expression, we addressed the molecular basis of the action of ghrelin in bone remodeling in vivo. We performed molecular, genetic and cell biological analyses of Ghsr-null mice and Ghsr-null mice with tissue specific Ghsr restoration. Furthermore, we evaluated the molecular mechanism of ghrelin by molecular and cell-based assays. Ghsr-null mice showed a low bone mass phenotype with poor bone formation. Restoring the expression of Ghsr specifically in osteoblasts, and not in osteoclasts or the central nervous system, ameliorated bone abnormalities in Ghsr-null mice. Cell-based assays revealed ghrelin induced the phosphorylation o...Continue Reading

References

Apr 1, 1993·Scandinavian Journal of Gastroenterology·P PerssonR Häkanson
Aug 5, 2003·Nature Reviews. Genetics·Steven L Teitelbaum, F Patrick Ross
Nov 12, 2003·Endocrine·Jesus P CamiñaFelipe F Casanueva
Apr 9, 2004·Proceedings of the National Academy of Sciences of the United States of America·Yuxiang SunRoy G Smith
Jan 12, 2005·The Journal of Endocrinology·Giuseppina MaccarinelliDaniela Cocchi
Mar 25, 2005·Physiological Reviews·Masayasu Kojima, Kenji Kangawa
Apr 13, 2005·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Nobuhiro FukushimaMasayasu Kojima
Aug 18, 2005·Obesity Surgery·F B LangerG Prager
Dec 3, 2005·The Journal of Clinical Investigation·Jeffrey M ZigmanJoel K Elmquist
Dec 3, 2005·The Journal of Clinical Investigation·Katherine E WortleyMark W Sleeman
Sep 18, 2007·Nature Medicine·Shingo SatoShu Takeda
Feb 26, 2008·Bone·Shu Takeda, Gerard Karsenty
Nov 13, 2009·Current Opinion in Endocrinology, Diabetes, and Obesity·Iris Pl WongHerbert Herzog
Mar 30, 2011·The Journal of Experimental Medicine·Daisuke KajimuraGerard Karsenty
Apr 27, 2011·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Shoshana M BartellClifton A Baile
Jun 28, 2011·The Journal of Clinical Investigation·Jen-Chieh ChuangJeffrey M Zigman
Jul 2, 2011·Molecular Endocrinology·Jen-Chieh ChuangJeffrey M Zigman
Apr 3, 2012·Endocrinology·Mone ZaidiJameel Iqbal
Jun 16, 2012·Endocrinology·Martijn van der VeldeJohannes P T M van Leeuwen
Sep 7, 2012·PloS One·Michael M ScottJeffrey M Zigman
Jan 5, 2013·Nutrition·Tulika AroraRaj Kumar Sharma
Feb 8, 2013·Nature Medicine·Roland Baron, Michaela Kneissel
Mar 28, 2013·The Journal of Clinical Endocrinology and Metabolism·Margaret C GarinAnne R Cappola
May 7, 2013·Nature·Toru FukudaHiroshi Itoh
Sep 7, 2013·Science·Vanessa K RidauraJeffrey I Gordon
Feb 26, 2014·Molecular Metabolism·Qian WangJeffrey M Zigman

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Citations

Jun 15, 2016·Medicinal Research Reviews·Zaid AmsoMargaret A Brimble
Apr 16, 2016·Nature Reviews. Rheumatology·Elena NeumannUlf Müller-Ladner
Jul 26, 2016·Frontiers in Physiology·Sonia Martínez-HerreroAlfredo Martínez
Jan 1, 2016·Biologie aujourd'hui·Alexandra Labarthe, Virginie Tolle
Oct 28, 2019·Bone Research·Jian LuoJianru Xiao
Aug 7, 2018·BioMed Research International·Hong-Gui YuYun-Jia Wang
Apr 20, 2021·International Journal of Clinical Practice·Sevgi ZorluOzlem Balci Ekmekci

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Methods Mentioned

BETA
PCR
ELISA

Software Mentioned

Comscan
BON RATOC
3D
Osteomeasure Analysis System ( Osteometrics )
TRI

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