RRC ID 42761
Author Kono SJ, Oshima Y, Hoshi K, Bonewald LF, Oda H, Nakamura K, Kawaguchi H, Tanaka S.
Title Erk pathways negatively regulate matrix mineralization.
Journal Bone
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.
Volume 40(1)
Pages 68-74
Published 2007-1
DOI 10.1016/j.bone.2006.07.024
PII S8756-3282(06)00629-6
PMID 16978937
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
IF 4.36
Times Cited 55
Human and Animal Cells