Reference - Detail
|Author||Kono SJ, Oshima Y, Hoshi K, Bonewald LF, Oda H, Nakamura K, Kawaguchi H, Tanaka S.|
|Title||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.
|MeSH||Actins / genetics Actins / metabolism Adenoviridae / genetics Animals Bone Matrix / chemistry Bone Matrix / enzymology* Calcification, Physiologic* / genetics Cells, Cultured Extracellular Signal-Regulated MAP Kinases / antagonists & inhibitors Extracellular Signal-Regulated MAP Kinases / genetics Extracellular Signal-Regulated MAP Kinases / physiology* Flavonoids / pharmacology Integrin-Binding Sialoprotein MAP Kinase Kinase 1 / genetics MAP Kinase Kinase 1 / metabolism Mice Osteoblasts / chemistry Osteoblasts / enzymology Osteopontin / genetics Osteopontin / metabolism Platelet-Derived Growth Factor / pharmacology Protein Kinase Inhibitors / pharmacology RNA, Messenger / analysis RNA, Messenger / metabolism Sialoglycoproteins / genetics Sialoglycoproteins / metabolism Skull / chemistry Skull / enzymology Skull / metabolism Transfection ras Proteins / genetics ras Proteins / metabolism|
|WOS Category||ENDOCRINOLOGY & METABOLISM|
|Human and Animal Cells|