



@article {2204,
	title = {Neuropeptide Y Y1 receptor antagonism increases bone mass in mice},
	journal = {BoneBone},
	volume = {51},
	year = {2012},
	note = {Export Date: 21 November 2012Source: ScopusCODEN: BONEDdoi: 10.1016/j.bone.2012.03.020PubMed ID: 22484690Language of Original Document: EnglishCorrespondence Address: Herzog, H.; Neuroscience Research Program, Garvan Institute of Medical Research, 384 Victoria St, Darlinghurst, Sydney, NSW 2010, Australia; email: h.herzog@garvan.org.auChemicals/CAS: corticosterone, 50-22-6; glucose, 50-99-7, 84778-64-3; n2 diphenylacetyl n (4 ureidomethylbenzyl)argininamide, 191868-14-1, 217977-06-5; neuropeptide Y, 82785-45-3, 83589-17-7; Arginine, 74-79-3; BIBO 3304; Glucose, 50-99-7; Receptors, Neuropeptide Y; neuropeptide Y-Y1 receptorTradenames: bibo 3304References: Karaguzel, G., Holick, M.F., Diagnosis and treatment of osteopenia (2010) Rev Endocr Metab Disord, 11, pp. 237-251;Burge, R., Dawson-Hughes, B., Solomon, D.H., Wong, J.B., King, A., Tosteson, A., Incidence and economic burden of osteoporosis-related fractures in the United States, 2005-2025 (2007) J Bone Miner Res, 22, pp. 465-475; 
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},
	month = {2012///},
	pages = {8 - 16},
	abstract = {The neuropeptide Y system has emerged as one of the major neural signalling pathways regulating bone homeostasis. Absence of Y1 receptor signalling from bone forming osteoblasts is responsible for an enhancement on bone mass in mice, suggesting that pharmacological blockade of Y1 receptors may offer a novel anabolic treatment option for improving bone mass. Here we show that oral administration of the selective Y1 receptor antagonist BIBO3304 for 8. weeks dose-dependently increases bone mass in mice. Histomorphometric analysis revealed a significant 1.5-fold increase in cancellous bone volume in the femora of mice treated with BIBO3304. Furthermore, bone microarchitecture was improved, with greater trabecular number and trabecular thickness. This increase in bone mass was associated with a significant increase in bone anabolic activity of osteoblasts and, interestingly, was evident despite a coincident increase in bone resorption, as evidenced by an increase in the number of the osteolytic osteoclasts. Changes were also evident in cortical bone, with a significant increase in periosteal mineral apposition rate. Importantly, no adverse extra-skeletal side effects were observed through Y1 receptor antagonism over the 8-week treatment period, with no effects of even the higher BIBO3304 dose on body weight, adiposity, energy metabolism or circulating corticosterone levels. Taken together, this work describes the first NPY-based anabolic treatment for improving bone mass, and highlights the therapeutic potential of blocking Y1 receptor signalling for the prevention of, or recovery from, degenerative skeletal diseases. {\textcopyright} 2012 Elsevier Inc.},
	keywords = {animal experiment, animal tissue, Animals, Arginine, article, body weight, Bone Density, bone mass, bone metabolism, bone strength, cancellous bone, controlled study, cortical bone, corticosterone, corticosterone blood level, dose response, Dose-Response Relationship, Drug, drug effect, drug mechanism, drug megadose, energy metabolism, femur, food intake, glucose, glucose homeostasis, Homeostasis, male, Mice, Mice, Inbred C57BL, morphometrics, mouse, n2 diphenylacetyl n (4 ureidomethylbenzyl)argininamide, neuropeptide Y, Neuropeptide yY, nonhuman, obesity, Oral drug administration, osteoblast, osteoclast activity, Osteogenesis, osteolysis, Osteopenia, Receptors, Neuropeptide Y, signal transduction, trabecular bone, Y1 receptor antagonism},
	isbn = {87563282 (ISSN)},
	url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-84859915620\&partnerID=40\&md5=29596d34bad3cbf751d1cbfadb63abb9},
	author = {Sousa, D.M. and Baldock, P.A. and Enriquez, R.F. and Zhang, L. and Sainsbury, A. and Lamghari, M. and Herzog, H.}
}
