



@article {2303,
	title = {NPY revealed as a critical modulator of osteoblast function in vitro: New insights into the role of Y1 and Y2 receptors},
	journal = {Journal of Cellular BiochemistryJ. Cell. Biochem.},
	volume = {107},
	year = {2009},
	note = {Cited By (since 1996): 12Export Date: 21 November 2012Source: ScopusCODEN: JCEBDdoi: 10.1002/jcb.22194PubMed ID: 19459152Language of Original Document: EnglishCorrespondence Address: Lamghari, M.; Instituto de Engenharia Biom{\'e}dica (INEB), Divis{\~a}o de Biomateriais, Universidade do Porto, Rua do Campo Alegre, 823, 4150-180 Porto, Portugal; email: lamghari@ineb.up.ptChemicals/CAS: calcium, 14092-94-5, 7440-70-2; osteoclast differentiation factor, 200145-93-3; osteoprotegerin, 205944-50-9; Alkaline Phosphatase, 3.1.3.1; Neuropeptide Y; Osteoprotegerin; RANK Ligand; Receptors, Neuropeptide YReferences: Ahmed, M., Srinivasan, G.R., Theodorsson, E., Bjurholm, A., Kreicbergs, A., Extraction and quantitation of neuropeptides in bone by radioimmunoassay (1994) Regul Pept, 51, pp. 179-188;Allison, S.J., Herzog, H., NPY and bone (2006) EXS, 95, pp. 171-182; 
Allison, S.J., Baldock, P., Sainsbury, A., Enriquez, R., Lee, N.J., Lin, E.J., Klugman, M., Gardiner, E.M., Conditional deletion of hypothalamic Y2 receptors reverts gonadectomy-induced bone loss in adult mice (2006) J Biol Chem, 281, pp. 23436-23444; 
Amano, S., Arai, M., Goto, S., Togari, A., Inhibitory effect of NPY on isoprenaline-induced osteoclastogenesis in mouse bone marrow cells (2007) Biochim Biophys Acta, 1770, pp. 966-973; 
Baldock, P.A., Sainsbury, A., Couzens, M., Enriquez, R.F., Ghomas, G.P., Gardiner, E.M., Herzog, H., Hypothalamic Y2 receptors regulate bone formation (2002) J Clin Investig, 109, pp. 915-921; 
Baldock, P.A., Sainsbury, A., Allison, S., Lin, E.J., Couzens, M., Boey, D., Enriquez, R., Gardiner, E.M., Hypothalamic control of bone formation: Distinct actions of leptin and y2 receptor pathways (2005) J Bone Miner Res, 20, pp. 1851-1857; 
Baldock, P.A., Allison, S.J., Lundberg, P., Lee, N.J., Slack, K., Lin, E.J., Enriquez, R.F., Herzog, H., Novel role of Y1 receptors in the coordinated regulation of bone and energy homeostasis (2007) J Biol Chem, 282, pp. 19092-19102; 
Chenu, C., Role of innervation in the control of bone remodelling (2004) J Musculoskel Neuron Interact, 4, pp. 132-134; 
Chenu, C., Marenzana, M., Sympathetic nervous system and bone remodeling (2005) Joint Bone Spine, 72, pp. 481-483; 
Clark, J.T., Kalra, P.S., Kalra, S.P., Neuropeptide Y stimulates feeding but inhibits sexual behavior in rats (1985) Endocrinology, 117, pp. 2435-2442; 
Dumont, Y., Jacques, D., Bouchard, P., Quirion, R., Species differences in the expression and distribution of the neuropeptide Y Y1, Y2, Y4, and Y5 receptors in rodents, guinea pig, and primates brains (1998) J Comp Neurol, 402, pp. 372-384; 
Elefteriou, F., Neuronal signalling and the regulation of bone remodelling (2005) Cell Mol Life Sci, 62, pp. 2339-2349; 
Ericsson, A., Schalling, M., McIntyre, K.R., Lundberg, J.M., Larhammar, D., Seroogy, K., Hokfelt, T., Persson, H., Detection of neuropeptide Y and its mRNA in megakaryocytes: Enhanced levels in certain autoimmune mice (1987) Proc Natl Acad Sci USA, 84, pp. 5585-5589; 
Fu, Q., Manolagas, S.C., O{\textquoteright}Brien, C.A., Parathyroid hormone controls receptor activator of NF-kappaB ligand gene expression via a distant transcriptional enhancer (2006) Mol Cell Biol, 26, pp. 6453-6468; 
Gori, F., Hofbauer, L.C., Dunstan, C.R., Spelsberg, T.C., Khosla, S., Riggs, B.L., The expression of osteoprotegerin and RANK ligand and the support of osteoclast formation by stromal-osteoblast lineage cells is developmentally regulated (2000) Endocrinology, 141, pp. 4768-4776; 
Herzog, H., Neuropeptide Y and energy homeostasis: Insights from Y receptor knockout models (2003) Eur J Pharmacol, 480 (1-3), pp. 21-29; 
Hill, E.L., Turner, R., Elde, R., Effects of neonatal sympathectomy and capsaicin treatment on bone remodeling in rats (1991) Neuroscience, 44 (3), pp. 747-755; 
Holliday, N.D., Michel, M.C., Cox, H.M., NPY receptor subtypes and their signal transduction (2004) Neuropeptide Y and related peptides, Handbook of experimental pharmacology, 162, pp. 45-74. , Michel MC, editor, Berlin: Springer-Verlag, Heidelberg, pp; 
Hosaka, H., Nagata, A., Yoshida, T., Shibata, T., Nagao, T., Tanaka, T., Saito, Y., Tatsuno, I., Pancreatic polypeptide is secreted from and controls differentiation through its specific receptors in osteoblastic MC3T3-E1 cells (2008) Peptides, 29 (8), pp. 1390-1395; 
Imai, S., Matsusue, Y., Neuronal regulation of bone metabolism and anabolism: Calcitonin gene-related peptide-, substance P-, and tyrosine hydroxylase-containing nerves and the bone (2002) Microsc Res Tech, 58, pp. 61-69; 
Kondo, H., Guo, J., Bringhurst, F.R., Cyclic adenosine monophosphate/protein kinase A mediates parathyroid hormone/parathyroid hormone-related protein receptor regulation of osteoclastogenesis and expression of RANKL and osteoprotegerin mRNAs by marrow stromal cells (2002) J Bone Miner Res, 17, pp. 1667-1679; 
Kuo, L.E., Kitlinska, J.B., Tilan, J.U., Li, L., Baker, S.B., Johnson, M.D., Lee, E.W., Zukowska, Z., Neuropeptide Y acts directly in the periphery on fat tissue and mediates stress-induced obesity and metabolic syndrome (2007) Nat Med, 13, pp. 803-811; 
Lee, S.K., Lornezo, J.A., Regulation of receptor activator of nuclear factor-kappaB ligand and osteoprotegerin mRNA expression by parathyroid hormone is predominantly mediated by the protein kinase a pathway in murine bone marrow cultures (2002) Bone, 31, pp. 252-259; 
Lerner, U.H., Lundberg, P., Kinins, neuro-osteogenic factors (2002) Principles of bone biology, pp. 773-799. , Bilezikian JP, Raisz LG, Rodan GA, editors, 2nd edition. San Diego: Academic Press. pp; 
Li, J., Ahmad, T., Spetea, M., Ahmed, M., Kreicbergs, A., Bone reinnervation after fracture: A study in the rat (2001) J Bone Miner Res, 16, pp. 1505-1510; 
Lundberg, P., Lerner, U.H., Expression and regulatory role of receptors for vasoactive intestinal peptide in bone cells (2002) Microsc Res Tech, 58, pp. 98-103; 
Lundberg, P., Bostr{\"o}m, I., Mukohyama, H., Bjurholm, A., Smans, K., Lerner, U.H., Neuro-hormonal control of bone metabolism: Vasoactive intestinal peptide stimulates alkaline phosphatase activity and mRNA expression in mouse calvarial osteoblasts as well as calcium accumulation mineralized bone nodules (1999) Regul Pept, 85, pp. 47-58; 
Lundberg, P., Allison, S.J., Lee, N.J., Baldock, P.A., Brouard, N., Rost, S., Enriquez, R.F., Herzog, H., Greater bone formation of Y2 knockout mice is associated with increased osteoprogenitor numbers and altered Y1 receptor expression (2007) J Biol Chem, 282, pp. 19082-19091; 
Michel, M.C., Beck-Sickinger, A., Cox, H., Doods, H.N., Herzog, H., Larhammar, D., Quirion, R., Westfall, T., XVI. International Union of Pharmacology recommendations for the nomenclature of neuropeptide Y, peptide YY, and pancreatic polypeptide receptors (1998) Pharmacol Rev, 50, pp. 143-150; 
Movafagh, S., Hobson, J.P., Spiegel, S., Kleinman, H.K., Zukowska, Z., Neuropeptide Y induces migration, proliferation, and tube formation of endothelial cells bimodallyvia Y1, Y2, and Y5 receptors (2006) FASEB J, 20, pp. 1327-1337; 
Sainsbury, A., Baldock, P.A., Schwarzer, C., Ueno, N., Enriquez, R.F., Couzens, M., Inui, A., Gardiner, E.M., Synergistic effects of Y2 and Y4 receptors on adiposity and bone mass revealed in double knockout mice (2003) Mol Cell Biol, 23, pp. 5225-5233; 
Serre, C.M., Farlay, D., Delmas, P.D., Chenu, C., Evidence for a dense and intimate innervation of the bone tissue, including glutamate-containing fibers (1999) Bone, 25, pp. 623-629; 
Simonet, W.S., Lacey, D.L., Dunstan, C.R., Kelley, M., Chang, M.S., L{\"u}thy, R., Nguyen, H.Q., Boyle, W.J., Osteoprotegerin: A novel secreted protein involved in the regulation of bone density (1997) Cell, 89, pp. 309-319; 
Sudo, H., Kodama, H.A., Amagai, Y., Yamamoto, S., Kasai, S., In vitro differentiation and calcification in a new clonal osteogenic cell line derived from newborn mouse calvaria (1983) J Cell Biol, 96, pp. 191-198; 
Szczesny, G., Molecular aspects of bone healing, remodelling (2002) Pol J Pathol, 53, pp. 145-153; 
Tatemoto, K., Neuropeptide Y: Complete amino acid sequence of the brain peptide (1982) Proc Natl Acad Sci USA, 79, pp. 5485-5489; 
Thiriet, N., Deng, X., Solinas, M., Ladenheim, B., Curtis, W., Goldberg, S.R., Palmiter, R.D., Cadet, J.L., Neuropeptide Y protects against methamphetamine-induced neuronal apoptosis in the mouse striatum (2005) J Neurosci, 25, pp. 5273-5279; 
Wittmann, W., Loacker, S., Kapeller, I., Herzog, H., Schwarzer, C., Y1-receptors regulate the expression of Y2-receptors in distinct mouse forebrain areas (2005) Neuroscience, 136, pp. 241-250; 
Wortley, K.E., Garcia, K., Okamoto, H., Thabet, K., Anderson, K.D., Shen, V., Herman, J.P., Sleeman, M.W., Peptide YY regulates bone turnover in rodents (2007) Gastroenterology, 133, pp. 1534-1543
},
	month = {2009///},
	pages = {908 - 916},
	abstract = {Neuropeptide Y (NPY) has recently emerged as a potential regulator of bone homeostasis. However, the relevance of NPY{\textquoteright}s role in osteoblast activity and the biological functions involving NPY receptors in bone homeostasis remain to be clarified. Here we report that chronically elevated NPY levels leaded to a modulation of the level of Y2 receptor expression marked with a transient down and upregulation according to the stage of osteoblast differentiation. We also show that NPY is a negative regulator of Y1 receptor expression. The pharmalogical activation of Y2 receptor with its agonist resulted in similar effect. Functional analysis also revealed the osteogenic potential of NPY with osteoblast phenotype markers being significantly enhanced in osteoprogenitor cells stimulated by NPY, probably due to the down-regulation of Y1 receptor. In contrasts, these cells exhibit a reduction in calcium deposition in extracellular matrix most likely mediated via Y2 receptor signalling. Furthermore, we show that NPY modulates receptor activator of nuclear factor kB (NF-kB) (RANK) ligand and osteoprotegerin, two key factors regulating bone remodelling. Specifically, NPY inhibits the transcriptional activity of RANKL promoter in osteoprogenitor cells and enhances OPG expression in osteoblasts at early stages of differentiation. However, NPY effect on OPG seemed to be unrelated to Y2 receptor activation. Taken together the present data supported the contribution of NPY pathway in bone homeostasis via a direct action on osteoblasts cells. {\textcopyright} 2009 Wiley-Liss, Inc.},
	keywords = {alkaline phosphatase, animal cell, animal tissue, Animals, article, Bone, Bone Marrow Cells, bone remodeling, Calcium, cell activity, cell differentiation, cell function, Cell Line, cell stimulation, controlled study, down regulation, extracellular matrix, gene expression regulation, genetic transcription, Homeostasis, immunoglobulin enhancer binding protein, in vitro study, Mice, neuropeptide Y, neuropeptide Y1 receptor, neuropeptide Y2 receptor, nonhuman, NPY, nuclear factor Y, osteoblast, Osteoblasts, osteoclast differentiation factor, Osteoprotegerin, phenotype, priority journal, promoter region, protein expression, RANK Ligand, Receptors, Neuropeptide Y, Reverse Transcriptase Polymerase Chain Reaction, signal transduction, stem cell, Stromal Cells, upregulation, Y1 receptor, Y2 receptor},
	isbn = {07302312 (ISSN)},
	url = {http://www.scopus.com/inward/record.url?eid=2-s2.0-67749108153\&partnerID=40\&md5=3fac97e90b88592291766e499000ae54},
	author = {Teixeira, L. and Sousa, D.M. and Nunes, A.F. and Sousa, M.M. and Herzog, H. and Lamghari, M.}
}
