Regulation of matrix Gla protein by @entity10173 in @entity19 osteoblast-like cells involves protein kinase A and XXXX pathways.

@entity9984 @entity10173 @entity5732 @entity45818 @entity19 @entity13438 @entity1359 @entity4515 @entity16699 @entity13436 @entity11009 @entity9501 @entity1928
Inhibition of osteoblast-mediated mineralization is one of the major catabolic effects of @entity10173 ( @entity10173 ) on bone. Previously, we showed that @entity10173 induces matrix @entity16699 ( @entity9984 ) protein ( @entity45818 ) expression and established that this induction is critical for @entity10173 -mediated inhibition of osteoblast mineralization. In the present study, we focus on the mechanism through which @entity10173 regulates @entity45818 expression in osteoblastic @entity19 cells. Following transient transfection of these cells with a -748 bp @entity19 @entity45818 promoter-luciferase construct (pMGP-luc), @entity10173 (10 (-7) M) induced promoter activity in a time-dependent manner with a maximal four- to six fold induction seen 6 h after @entity10173 treatment. Both @entity9501 (PKA inhibitor) and @entity5732 ( @entity13438 inhibitor), suppressed @entity10173 induction of @entity45818 promoter activity as well as the @entity45818 mRNA level. In addition, @entity1928 (PKA activator) stimulated @entity45818 promoter activity and mRNA levels confirming that PKA is one of the signaling molecules required for regulation of @entity45818 by @entity10173 . Co-transfection of @entity19 cells with pMGP-luc and @entity13438 (SP), a plasmid encoding the constitutively active form of @entity13438 , led to a dose-dependent increase in @entity45818 promoter activity. Both @entity45818 promoter activity and @entity45818 mRNA level were not affected by the protein kinase C (PKC) inhibitor, @entity11009 . However, @entity1359 ( @entity4515 ), a selective PKC activator induced @entity45818 mRNA expression through activation of @entity13436 ( @entity13436 ). Taken together, these results indicate that @entity10173 regulates @entity45818 via both PKA- and @entity13436 -dependent pathways.
