Erk pathways negatively regulate matrix mineralization.
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.
Kono
Shin-jiro
SJ
Department of Orthopaedic Surgery, Faculty of Medicine, The University of Tokyo, 7-3-1 Hongo, Tokyo 113-0033, Japan.
Oshima
Yasushi
Y
Hoshi
Kazuto
K
Bonewald
Lynda F
LF
Oda
Hiromi
H
Nakamura
Kozo
K
Kawaguchi
Hiroshi
H
Tanaka
Sakae
S
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
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