title: Arginase 1 is a negative regulator of osteoclast differentiation.
abstract: Arginase 1 (Arg1) limits the availability of l-arginine for producing nitric oxide (NO) and ornithine, a substrate for polyamine synthesis. Anti-osteoclastogenic activities of NO and polyamines, and the involvement of Arg1 on the dendritic cell differentiation of dendritic cells have been reported, but the relevance of Arg1 to osteoclast differentiation has not been investigated. Here, we observed Arg1 down-regulation during the RANKL-induced differentiation of bone marrow-derived macrophages into osteoclasts. Arg1 overexpression significantly inhibited osteoclast differentiation with low NO production, while Arg1 knockdown enhanced osteoclast differentiation with high NO production. These results suggest that Arg1 and NO have reciprocal roles as negative and positive regulators, respectively, of osteoclast differentiation. We conclude that Arg1 is down-regulated during osteoclast differentiation and may negatively regulate osteoclast differentiation by regulating NO production.
authors.affiliation: Research Institute of Basic Science, Sunchon National, University, Suncheon 540‑742, Republic of Korea.
authors.forename: Jeong-Tae
authors.initials: JT
authors.lastname: Yeon
authors.forename: Sik-Won
authors.initials: SW
authors.lastname: Choi
authors.forename: Seong Hwan
authors.initials: SH
authors.lastname: Kim
mesh_terms: D000818:Animals; D001119:Arginase / Q000235:genetics* / Q000378:metabolism; D001120:Arginine / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology; D001862:Bone Resorption / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics*; D002478:Cells, Cultured; D015536:Down-Regulation; D006410:Hematopoiesis / Q000235:genetics*; D008264:Macrophages / Q000166:cytology*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009569:Nitric Oxide / Q000096:biosynthesis; D009952:Ornithine / Q000096:biosynthesis; D010010:Osteoclasts / Q000166:cytology*; D053245:RANK Ligand / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction
chemical_list: D053245:RANK Ligand; D034741:RNA, Small Interfering; C505689:Tnfsf11 protein, mouse; D009569:Nitric Oxide; D001120:Arginine; D009952:Ornithine; C544448:Arg1 protein, mouse; D001119:Arginase