title: Erk pathways negatively regulate matrix mineralization.
abstract: Skeletal mineralization is an important step regulating the mechanical properties of the calcified tissues, but molecular events underlying mineralization still remain elusive. We examined the role of extracellular signal-regulated kinase (Erk) pathways in matrix mineralization of osteogenic cells both in vitro and in vivo. Matrix mineralization by preosteocytic MLO-A5 cells and osteoblastic MC3T3-E1 cells was increased by either PD98059 Mek inhibitor treatment or adenovirus vector-mediated dominant negative Ras (Ras(DN)) expression and was suppressed by Erk activation by platelet-derived growth factor (PDGF) treatment or constitutively active Mek1 (Mek(CA)) expression. Administration of adenovirus vectors carrying Ras(DN) gene onto the calvaria of 1-day-old mice increased the mineralization of the tissues, while that of the Mek(CA) adenovirus suppressed it. These results suggest that the Erk pathway is a negative regulator of the matrix mineralization both in vitro and in vivo.
authors.affiliation: Department of Orthopaedic Surgery, Faculty of Medicine, The University of Tokyo, 7-3-1 Hongo, Tokyo 113-0033, Japan.
authors.forename: Shin-jiro
authors.initials: SJ
authors.lastname: Kono
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Oshima
authors.forename: Kazuto
authors.initials: K
authors.lastname: Hoshi
authors.forename: Lynda F
authors.initials: LF
authors.lastname: Bonewald
authors.forename: Hiromi
authors.initials: H
authors.lastname: Oda
authors.forename: Kozo
authors.initials: K
authors.lastname: Nakamura
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kawaguchi
authors.forename: Sakae
authors.initials: S
authors.lastname: Tanaka
mesh_terms: D000199:Actins / Q000235:genetics / Q000378:metabolism; D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D001857:Bone Matrix / Q000737:chemistry / Q000201:enzymology*; D002113:Calcification, Physiologic / Q000235:genetics; D002478:Cells, Cultured; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D005419:Flavonoids / Q000494:pharmacology; D058574:Integrin-Binding Sialoprotein; D048369:MAP Kinase Kinase 1 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D010006:Osteoblasts / Q000737:chemistry / Q000201:enzymology; D053495:Osteopontin / Q000235:genetics / Q000378:metabolism; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D012795:Sialoglycoproteins / Q000235:genetics / Q000378:metabolism; D012886:Skull / Q000737:chemistry / Q000201:enzymology / Q000378:metabolism; D014162:Transfection; D018631:ras Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D000199:Actins; D005419:Flavonoids; C546872:Ibsp protein, mouse; D058574:Integrin-Binding Sialoprotein; D010982:Platelet-Derived Growth Factor; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; D012795:Sialoglycoproteins; D053495:Osteopontin; D048049:Extracellular Signal-Regulated MAP Kinases; D048369:MAP Kinase Kinase 1; D018631:ras Proteins; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one