Inhibitory effect of NPY on isoprenaline-induced osteoclastogenesis in mouse bone marrow cells.
The effect of neuropeptide Y (NPY), a co-transmitter with noradrenaline in peripheral sympathetic nerve fibers, on the osteoclastogenesis in mouse bone marrow cell cultures treated with isoprenaline, a beta-adrenergic receptor (beta-AR) agonist, was examined. The mouse bone marrow cells constitutively expressed mRNAs for the NPY-Y1 receptor and beta2-AR. NPY inhibited the formation of osteoclast-like cells induced by isoprenaline but not that by 1alpha,25-dihydroxyvitamin D3 (1alpha,25(OH)2D3) or soluble receptor activator of nuclear factor-kappaB ligand (RANKL); and it suppressed the production of RANKL and cyclic AMP (cAMP) increased by isoprenaline but not those increased by 1alpha,25(OH)2D3. NPY also inhibited osteoclastogenesis induced by forskolin, an activator of adenylate cyclase; however, it did not inhibit that induced by exogenously supplied dibutyryl cAMP, a cell-permeable cAMP analog that activates cAMP-dependent protein kinase. These results demonstrate that NPY inhibited the isoprenaline-induced osteoclastogenesis by blocking the agonist-elicited increases in the production of cAMP and RANKL in mouse bone marrow cells, suggesting an interaction between NPY and beta-AR agonist in bone resorption.
Amano
Shinobu
S
Department of Pharmacology, School of Dentistry, Aichi-Gakuin University, Nagoya 464-8650, Japan.
Arai
Michitsugu
M
Goto
Shigemi
S
Togari
Akifumi
A
D000067956:Adenylyl Cyclase Inhibitors; D000262:Adenylyl Cyclases / Q000378:metabolism; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000378:metabolism*; D001862:Bone Resorption / Q000378:metabolism*; D003994:Bucladesine / Q000378:metabolism / Q000494:pharmacology; D002117:Calcitriol / Q000378:metabolism / Q000494:pharmacology; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D007545:Isoproterenol / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008817:Mice, Mutant Strains; D009478:Neuropeptide Y / Q000378:metabolism / Q000494:pharmacology*; D010010:Osteoclasts / Q000166:cytology / Q000378:metabolism*; D053245:RANK Ligand / Q000378:metabolism; D018343:Receptors, Adrenergic, beta-2; D017476:Receptors, Neuropeptide Y / Q000819:agonists / Q000378:metabolism; D014815:Vitamins / Q000378:metabolism / Q000494:pharmacology
D000067956:Adenylyl Cyclase Inhibitors; D000318:Adrenergic beta-Agonists; D009478:Neuropeptide Y; D053245:RANK Ligand; D018343:Receptors, Adrenergic, beta-2; D017476:Receptors, Neuropeptide Y; C505689:Tnfsf11 protein, mouse; D014815:Vitamins; C097212:neuropeptide Y-Y1 receptor; D005576:Colforsin; D003994:Bucladesine; D000262:Adenylyl Cyclases; D002117:Calcitriol; D007545:Isoproterenol