First Author | Ge C | Year | 2007 |
Journal | J Cell Biol | Volume | 176 |
Issue | 5 | Pages | 709-18 |
PubMed ID | 17325210 | Mgi Jnum | J:119821 |
Mgi Id | MGI:3703303 | Doi | 10.1083/jcb.200610046 |
Citation | Ge C, et al. (2007) Critical role of the extracellular signal-regulated kinase-MAPK pathway in osteoblast differentiation and skeletal development. J Cell Biol 176(5):709-18 |
abstractText | The extracellular signal-regulated kinase (ERK)-mitogen-activated protein kinase (MAPK) pathway provides a major link between the cell surface and nucleus to control proliferation and differentiation. However, its in vivo role in skeletal development is unknown. A transgenic approach was used to establish a role for this pathway in bone. MAPK stimulation achieved by selective expression of constitutively active MAPK/ERK1 (MEK-SP) in osteoblasts accelerated in vitro differentiation of calvarial cells, as well as in vivo bone development, whereas dominant-negative MEK1 was inhibitory. The involvement of the RUNX2 transcription factor in this response was established in two ways: (a) RUNX2 phosphorylation and transcriptional activity were elevated in calvarial osteoblasts from TgMek-sp mice and reduced in cells from TgMek-dn mice, and (b) crossing TgMek-sp mice with Runx2+/- animals partially rescued the hypomorphic clavicles and undemineralized calvaria associated with Runx2 haploinsufficiency, whereas TgMek-dn; Runx2+/- mice had a more severe skeletal phenotype. This work establishes an important in vivo function for the ERK-MAPK pathway in bone that involves stimulation of RUNX2 phosphorylation and transcriptional activity. |