Critical role of the extracellular signal-regulated kinase-MAPK pathway in osteoblast differentiation and skeletal development.
Critical role of the extracellular signal-regulated kinase-MAPK pathway in osteoblast differentiation and skeletal development.
复制标题
DOI：
10.1083/jcb.200610046
复制
发表时间：
2007-02-26
期刊：
影响因子：
--
通讯作者：
Franceschi RT
中科院分区：
文献类型：
--
作者：
Ge C;Xiao G;Jiang D;Franceschi RT
细胞外信号调节激酶（ERK）-丝裂原活化蛋白激酶（MAPK）途径在细胞表面和细胞核之间提供了控制增殖和分化的主要联系。然而，其在骨骼发育中的体内作用尚不清楚。一种转基因方法被用来建立该途径在骨中的作用。MAPK的刺激实现了选择性表达的组成型活性MAPK/ERK 1（MEK-SP）在成骨细胞加速在体外分化的颅骨细胞，以及在体内骨发育，而显性阴性MEK 1是抑制性的。RUNX 2转录因子参与该反应的方式有两种：（a）TgMek-sp小鼠的颅骨成骨细胞中RUNX 2磷酸化和转录活性升高，而TgMek-dn小鼠的细胞中RUNX 2磷酸化和转录活性降低，以及（B）将TgMek-sp小鼠与Runx 2 +/-动物杂交，部分挽救了与Runx 2单倍性不足相关的低形态锁骨和未矿化的颅骨，而TgMek-dn小鼠的细胞中RUNX 2磷酸化和转录活性降低。Runx 2 +/−小鼠具有更严重的骨骼表型。这项工作建立了骨中ERK-MAPK通路的重要体内功能，该通路涉及刺激RUNX 2磷酸化和转录活性。
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.
登录
查看更多内容
影响因子：
4.8
作者：
Celil, AB;Campbell, PG
通讯作者：
Campbell, PG
影响因子：
2.2
作者：
Nakayama, A;Yokojima, S
通讯作者：
Yokojima, S
影响因子：
5.6
作者：
OWEN, TA;ARONOW, M;STEIN, GS
通讯作者：
STEIN, GS
影响因子：
10.5
作者：
Murakami, S;Balmes, G;de Crombrugghe, B
通讯作者：
de Crombrugghe, B
Osf2/Cbfa1：成骨细胞分化的转录激活因子
影响因子：
64.5
作者：
Ducy, P;Zhang, R;Karsenty, G
通讯作者：
Karsenty, G