title: Autocrine effects of neuromedin B stimulate the proliferation of rat primary osteoblasts.
abstract: Neuromedin B (NMB) is a mammalian bombesin-like peptide that regulates exocrine/endocrine secretion, smooth muscle contraction, body temperature, and the proliferation of some cell types. Here, we show that mRNA encoding Nmb and its receptor (Nmbr) are expressed in rat bone tissue. Immunohistochemical analysis demonstrated that NMB and NMBR colocalize in osteoblasts, epiphyseal chondrocytes, and proliferative chondrocytes of growth plates from mouse hind limbs. Then, we investigated the effect of NMB on the proliferation of rat primary cultured osteoblasts. Proliferation assays and 5-bromo-2'-deoxyuridine incorporation assays demonstrated that NMB augments the cell number and enhances DNA synthesis in osteoblasts. Pretreatment with the NMBR antagonist BIM23127 inhibited NMB-induced cell proliferation and DNA synthesis. Western blot analysis showed that NMB activates ERK1/2 MAPK signaling in osteoblasts. Pretreatment with the MAPK/ERK kinase inhibitor U0126 attenuated NMB-induced cell proliferation and DNA synthesis. We also investigated the effects of molecules that contribute to osteoblast proliferation and differentiation on Nmb expression in osteoblasts. Real-time PCR analysis demonstrated that 17β-estradiol (E2) and transforming growth factor β1 increase and decrease Nmb mRNA expression levels respectively. Finally, proliferation assays revealed that the NMBR antagonist BIM23127 suppresses E2-induced osteoblast proliferation. These results suggest that NMB/NMBR signaling plays an autocrine or paracrine role in osteoblast proliferation and contributes to the regulation of bone formation.
authors: Department of Pharmacology, Graduate School of Medical and Dental Science, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan.
authors: Hiroki
authors: H
authors: Saito
authors: Tomoya
authors: T
authors: Nakamachi
authors: Kazuhiko
authors: K
authors: Inoue
authors: Ryuji
authors: R
authors: Ikeda
authors: Kazuo
authors: K
authors: Kitamura
authors: Naoto
authors: N
authors: Minamino
authors: Seiji
authors: S
authors: Shioda
authors: Atsuro
authors: A
authors: Miyata
mesh_terms: D000818:Animals; D019898:Autocrine Communication / Q000502:physiology*; D002070:Butadienes / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism; D015287:Neurokinin B / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D009570:Nitriles / Q000494:pharmacology; D010006:Osteoblasts / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D010456:Peptides, Cyclic / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018004:Receptors, Bombesin / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology
chemical_list: C092829:BIM 23127; D002070:Butadienes; D004791:Enzyme Inhibitors; D009570:Nitriles; D010456:Peptides, Cyclic; D018004:Receptors, Bombesin; D053773:Transforming Growth Factor beta1; C113580:U 0126; D004958:Estradiol; D015287:Neurokinin B; C038393:neuromedin B; D020929:Mitogen-Activated Protein Kinase Kinases