Extracellular Signal-Regulated Kinase 1 (ERK1) and ERK2 Play Essential Roles in Osteoblast Differentiation and in Supporting Osteoclastogenesis
Extracellular Signal-Regulated Kinase 1 (ERK1) and ERK2 Play Essential Roles in Osteoblast Differentiation and in Supporting Osteoclastogenesis
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DOI：
10.1128/mcb.01549-08
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发表时间：
2009-11-01
影响因子：
5.3
通讯作者：
Murakami, Shunichi
中科院分区：
文献类型：
--
作者：
Matsushita, Takehiko;Chan, Yuk Yu;Murakami, Shunichi
成骨细胞和软骨细胞起源于普通的骨软骨祖细胞。我们在这里表明，ERK1和ERK2在骨软骨祖细胞的失活，导致成骨细胞分化的阻滞，并导致异位软骨分化的骨形成区域的软骨膜。此外，间充质细胞中促分裂原活化蛋白激酶信号的增加增强了成骨细胞分化并抑制了软骨细胞分化。这些观察结果表明，细胞外信号调节激酶1（ERK 1）和ERK 2在间充质细胞的谱系特化中发挥重要作用。ERK1和ERK2的失活导致β-连环蛋白表达减少，表明经典Wnt信号在骨骼谱系特化的ERK1和ERK2调节中的作用。此外，ERK1和ERK2的失活显著降低了RANKL表达，导致破骨细胞形成延迟。因此，我们的研究结果表明，ERK1和ERK2不仅在骨软骨祖细胞的谱系特化中发挥重要作用，而且还支持体内破骨细胞的形成。
Osteoblasts and chondrocytes arise from common osteo-chondroprogenitor cells. We show here that inactivation of ERK1 and ERK2 in osteo-chondroprogenitor cells causes a block in osteoblast differentiation and leads to ectopic chondrogenic differentiation in the bone-forming region in the perichondrium. Furthermore, increased mitogen-activated protein kinase signaling in mesenchymal cells enhances osteoblast differentiation and inhibits chondrocyte differentiation. These observations indicate that extracellular signal-regulated kinase 1 (ERK1) and ERK2 play essential roles in the lineage specification of mesenchymal cells. The inactivation of ERK1 and ERK2 resulted in reduced beta-catenin expression, suggesting a role for canonical Wnt signaling in ERK1 and ERK2 regulation of skeletal lineage specification. Furthermore, inactivation of ERK1 and ERK2 significantly reduced RANKL expression, accounting for a delay in osteoclast formation. Thus, our results indicate that ERK1 and ERK2 not only play essential roles in the lineage specification of osteo-chondroprogenitor cells but also support osteoclast formation in vivo.