Increased sphingosine-1-phosphate production in response to osteocyte mechanotransduction.
Increased sphingosine-1-phosphate production in response to osteocyte mechanotransduction.
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DOI：
10.1016/j.bonr.2017.10.002
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发表时间：
2017-12
期刊：
影响因子：
2.5
通讯作者：
Gooi JH
中科院分区：
文献类型：
--
作者：
Dobrosak C;Gooi JH
在过去的几年里，人们对脂质介质鞘氨醇-1-磷酸（S1 P）如何影响骨稳态的兴趣大大增加。最近的工作已经假设了S1 P对成骨细胞和破骨细胞的多种作用。基于这些发现，S1 P被认为是一种潜在的骨质疏松症治疗方法。然而，迄今为止，只有一项研究调查了协调骨代谢的细胞中的S1 P信号传导：骨细胞。本研究旨在阐明S1 P信号在骨细胞力学信号转导中的作用。利用3D细胞培养，我们建立了Ocy 454骨细胞系中与S1 P信号系统相关的所有基因的表达谱。暴露于机械负荷导致Sost，Spns 2，S1 P转运蛋白，Sgpl 1和Sgppl 1的下调，负责降解和去磷酸化的S1 P的酶。这些发现，与流体流诱导的Sphk 1，负责磷酸化的鞘氨醇激酶的上调，表明骨细胞的机械刺激导致细胞内S1 P的增加。这通过机械加载Ocy 454细胞快速增加条件培养基和蛋白质裂解物中的S1 P产生来证实。这些研究结果强烈表明S1 P在骨的机械负荷反应中起重要作用。骨细胞在整个骨骼中形成细胞网络，非常适合感知骨骼的需求并对其做出反应。在过去的几年里，人们对S1 P如何影响骨稳态的兴趣大大增加。暴露于机械负荷显著改变骨细胞S1 P信号传导。这表明S1 P的产生在骨对机械负荷的响应中起重要作用。
Over the past few years interest has greatly increased in how the lipid mediator sphingosine-1-phosphate (S1P) influences bone homeostasis. Recent work has postulated multiple effects of S1P on osteoblasts and osteoclasts. Based on these findings, S1P has been proposed as a potential osteoporosis treatment. However, to date, there has been only a single study investigating S1P signalling in the cells that co-ordinate bone metabolism: osteocytes. This study aimed to elucidate the role of S1P signalling in osteocyte mechanotransduction. Utilising 3D cell culture we established the expression profile of all genes related to the S1P signalling system in the Ocy454 osteocyte cell line. Exposure to mechanical loading resulted in a downregulation in Sost, Spns2, the S1P transporter, Sgpl1 and Sgppl1 the enzymes responsible for degradation and dephosphorylation of S1P. These findings, in conjunction with fluid-flow induced upregulation of Sphk1, the kinase responsible for phosphorylation of sphingosine, suggest that mechanical stimulation of osteocytes leads to an increase in intracellular S1P. This was confirmed with mechanical loading of Ocy454 cells rapidly increasing S1P production in conditioned media and protein lysates. These findings strongly suggest an important role for S1P in the response to mechanical loading of bone. Osteocytes form a cellular network throughout bone ideally suited for sensing the needs of the skeleton and responding to them. Over the past few years interest has greatly increased in how S1P influences bone homeostasis. Exposure to mechanical loading significantly modifies osteocyte S1P signalling. This suggests an important role for S1P production in the response to mechanical loading of bone.