Osteoblasts secrete a complex extracellular matrix (ECM) containing collagenous and noncollagenous proteins, bone morphogenetic proteins (BMPs), and growth factors. Osteoblast-specific gene expression requires @entity620 (AA)-dependent assembly of a collagenous ECM. Matrix responsiveness requires an alpha2beta1 integrin-collagen interaction and mitogen-activated protein kinase (MAPK) activity, which phosphorylates and activates the osteoblast-specific transcription factor @entity2447 . This study examines interactions between this integrin/MAPK-mediated pathway and signals initiated by BMPs contained in the osteoblast matrix. @entity19 cells were shown to constitutively express @entity8385 , @entity7739 , and @entity17736 . @entity13421 , a specific BMP inhibitor, reversibly blocked AA-induced gene expression, indicating that BMP production by @entity19 cells was necessary for differentiation. The ability of exogenously added @entity8385 , @entity7739 , or @entity17736 to stimulate @entity2450 ( @entity2450 ) and bone sialoprotein (BSP) mRNAs or @entity2450 promoter activity was synergistically increased in cells that were actively synthesizing an ECM (i.e., were grown in the presence of AA). A minimum of 4 days of ECM accumulation was required for this synergistic response to be observed. Neither @entity17736 , AA, nor a combination of these two treatments had major effects on @entity2447 messenger RNA (mRNA) or protein levels, as would be expected if regulation was mainly at the posttranscriptional level. @entity5732 , a specific inhibitor of MAPK/ @entity13436 (MEK), blocked AA- or @entity17736 /AA-dependent gene expression in a time- and dose-dependent manner that was closely correlated with inhibition of @entity13436 ( @entity13436 ) phosphorylation. This work establishes that autocrine BMP production as well as integrin-mediated cell-collagen interactions are both required for osteoblast differentiation, and both these pathways require MAP kinase activity.

Bone morphogenetic proteins, extracellular matrix, and mitogen-activated protein kinase signaling pathways are required for osteoblast-specific gene expression and differentiation in XXXX cells.

@entity5732 :: ('MESH:C113580', 'Chemical') :: ['U0126'] @entity2447 :: ('12393(Tax:10090)', 'Gene') :: ['Cbfa1'] @entity620 :: ('MESH:D001205', 'Chemical') :: ['ascorbic acid'] @entity19 :: ('10090', 'Species') :: ['MC3T3-E1'] @entity2450 :: ('12097(Tax:10090)', 'Gene') :: ['OCN', 'osteocalcin'] @entity17736 :: ('12162(Tax:10090)', 'Gene') :: ['BMP-7'] @entity13421 :: ('18121(Tax:10090)', 'Gene') :: ['Noggin'] @entity8385 :: ('12156(Tax:10090)', 'Gene') :: ['BMP-2'] @entity13436 :: ('26413(Tax:10090)', 'Gene') :: ['ERK', 'extracellular signal-regulated kinase'] @entity7739 :: ('12159(Tax:10090)', 'Gene') :: ['BMP-4']
@entity19 :: (10090,Species) :: ['MC3T3-E1']
