Control of Osteoblast-Specific Gene Expression by the Extracellular Matrix Environment
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概要
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Osteoblast precursors must synthesize a collagenous extracellular matrix (ECM) before they will differentiate. A cell : ECM interaction mediated by integrin cell surface receptors is essential for induction of osteocalcin and other osteoblast-related proteins. This interaction stimulates the binding of the bone-specific transcription factor, Runx 2/Cbfa 1, to the osteocalcin promoter through a mechanism involving activation of the MEK/ERK branch of the mitogen-activated protein kinase (MAPK) pathway and Runx 2/Cbfa 1 phosphorylation. Other inducers of MAPK activity such as FGF2 and mechanical loading of cells also stimulate Runx 2/Cbfa 1 phosphorylation and transcriptional activity. Furthermore, ECM/MAPK-derived signals are required for bone morphogenetic proteins (BMPs) to be fully active in stimulating osteoblast gene expression. These results suggest a general model in which MAPK activity and Runx 2/Cbfa 1 phosphorylation are critical for the transcriptional activity of this molecule. Phosphorylated Runx 2/Cbfa 1 may exhibit increased affinity for specific enhancer elements in target genes and for accessory nuclear proteins. However, the precise mechanism involved in its activation is not fully understood.
- 日本結合組織学会の論文
- 2003-09-25
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関連論文
- Control of Osteoblast-Specific Gene Expression by the Extracellular Matrix Environment
- Control of Osteoblast-Specific Gene Expression by the Extracellular Matrix Environment