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Transcriptional Regulation of Osteoblasts
Author(s) -
FRANCESCHI RENNY T.,
GE CHUNXI,
XIAO GUOZHI,
ROCA HERNAN,
JIANG DI
Publication year - 2007
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1402.081
Subject(s) - runx2 , microbiology and biotechnology , phosphorylation , mesenchymal stem cell , mapk/erk pathway , transcription factor , chondrogenesis , atf4 , chemistry , signal transduction , biology , biochemistry , gene
: The differentiation of osteoblasts from mesenchymal precursors requires a series of cell fate decisions controlled by a hierarchy of transcription factors. Among these are RUNX2, Osterix (OSX), ATF4, and a large number of nuclear coregulators. During bone development, initial RUNX2 expression coincides with the formation of mesenchymal condensations well before the branching of chondrogenic and osteogenic lineages. Given that RUNX2 is expressed so early and participates in several stages of bone formation, it is not surprising that it is subject to a variety of controls. These include regulation by nuclear accessory factors and posttranslational modification, especially phosphorylation. Specific examples of RUNX2 regulation include interactions with DLX proteins and ATF4 and phosphorylation by the ERK/MAP kinase pathway. RUNX2 is regulated via phosphorylation of critical serine residues in the P/S/T domain. MAPK activation of RUNX2 was also found to occur in vivo . Transgenic expression of constitutively active MEK1 in osteoblasts accelerated skeletal development while a dominant‐negative MEK1 retarded development in a RUNX2‐dependent manner. These studies allow us to begin understanding the complex mechanisms necessary to fine‐tune bone formation in response to extracellular stimuli including ECM interactions, mechanical loads, and hormonal stimulation.