Sphingosine 1-Phosphate (S1P) Receptors 1 and 2 Coordinately Induce Mesenchymal Cell Migration through S1P Activation of Complementary Kinase Pathways
Sphingosine 1-Phosphate (S1P) Receptors 1 and 2 Coordinately Induce Mesenchymal Cell Migration through S1P Activation of Complementary Kinase Pathways
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DOI：
10.1074/jbc.m112.413583
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发表时间：
2013-02-22
影响因子：
4.8
通讯作者：
Oursler, Merry Jo
中科院分区：
文献类型：
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作者：
Quint, Patrick;Ruan, Ming;Oursler, Merry Jo
正常的骨转换需要骨吸收和骨形成的紧密耦合，以保持骨量和结构。随着年龄的增长和在一些病理条件下，这种耦合打破，导致净骨丢失或过量骨形成。为了保持或恢复正常的骨代谢，确定破骨细胞和成骨细胞前体相互作用并促进偶联的机制至关重要。我们发现破骨细胞产生趋化因子鞘氨醇1-磷酸（S1 P），刺激成骨细胞迁移。因此，破骨细胞衍生的S1 P可以将成骨细胞募集到骨吸收位点，作为替换丢失的骨的初始步骤。在这项研究中，我们研究了S1 P刺激间充质（骨骼）细胞趋化性的机制。S1 P处理间充质（骨骼）细胞激活RhoA GTdR，但这种小G蛋白并不有助于迁移。相反，两种S1 P受体S1 PR 1和S1 PR 2分别通过激活JAK/STAT 3和FAK/PI 3 K/AKT信号通路协调促进迁移。这些数据表明，趋化因子S1 P通过激活激酶信号通路将骨形成与骨吸收偶联。
Normal bone turnover requires tight coupling of bone resorption and bone formation to preserve bone quantity and structure. With aging and during several pathological conditions, this coupling breaks down, leading to either net bone loss or excess bone formation. To preserve or restore normal bone metabolism, it is crucial to determine the mechanisms by which osteoclasts and osteoblast precursors interact and contribute to coupling. We showed that osteoclasts produce the chemokine sphingosine 1-phosphate (S1P), which stimulates osteoblast migration. Thus, osteoclast-derived S1P may recruit osteoblasts to sites of bone resorption as an initial step in replacing lost bone. In this study we investigated the mechanisms by which S1P stimulates mesenchymal (skeletal) cell chemotaxis. S1P treatment of mesenchymal (skeletal) cells activated RhoA GTPase, but this small G protein did not contribute to migration. Rather, two S1P receptors, S1PR1 and S1PR2, coordinately promoted migration through activation of the JAK/STAT3 and FAK/PI3K/AKT signaling pathways, respectively. These data demonstrate that the chemokine S1P couples bone formation to bone resorption through activation of kinase signaling pathways.