The roles of P2Y2 purinergic receptors in osteoblasts and mechanotransduction.
The roles of P2Y2 purinergic receptors in osteoblasts and mechanotransduction.
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DOI：
10.1371/journal.pone.0108417
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
You J
中科院分区：
文献类型：
--
作者：
Xing Y;Gu Y;Bresnahan JJ;Paul EM;Donahue HJ;You J
我们以前证明，使用成骨细胞MC 3 T3-E1细胞，P2 Y2嘌呤能受体参与成骨细胞机械转导。在这项研究中，我们的目标是进一步调查，使用敲除小鼠模型，P2 Y2受体在骨机械生物学的作用。我们首先在野生型小鼠和P2 Y2基因敲除小鼠中用micro-CT检查骨结构并用三点弯曲实验测量骨机械性能。我们发现来自P2 Y2基因敲除小鼠的骨在17周龄时具有显著降低的骨体积、骨厚度、骨刚度和骨极限断裂力。为了阐明P2 Y2受体促进骨生物学的机制，我们研究了野生型和P2 Y2基因敲除小鼠骨髓细胞的分化和矿化。我们发现，P2 Y2受体缺陷减少骨髓细胞的分化和矿化。接下来，我们比较了野生型和P2 Y2敲除小鼠的原代成骨细胞对ATP和机械刺激（振荡流体流）的反应，发现野生型小鼠的成骨细胞在ERK 1/2磷酸化方面对ATP和流体流的反应比P2 Y2敲除小鼠更强。然而，我们没有检测到野生型和P2 Y2敲除成骨细胞之间响应于流体流动的ATP释放的任何差异。我们的研究结果表明，P2 Y2受体在骨髓细胞分化和矿化以及骨细胞力学转导中起重要作用，导致P2 Y2基因敲除小鼠的骨质减少表型。
We previously demonstrated, using osteoblastic MC3T3-E1 cells, that P2Y2 purinergic receptors are involved in osteoblast mechanotransduction. In this study, our objective was to further investigate, using a knockout mouse model, the roles of P2Y2 receptors in bone mechanobiology. We first examined bone structure with micro-CT and measured bone mechanical properties with three point bending experiments in both wild type mice and P2Y2 knockout mice. We found that bones from P2Y2 knockout mice have significantly decreased bone volume, bone thickness, bone stiffness and bone ultimate breaking force at 17 week old age. In order to elucidate the mechanisms by which P2Y2 receptors contribute to bone biology, we examined differentiation and mineralization of bone marrow cells from wild type and P2Y2 knockout mice. We found that P2Y2 receptor deficiency reduces the differentiation and mineralization of bone marrow cells. Next, we compared the response of primary osteoblasts, from both wild type and P2Y2 knockout mice, to ATP and mechanical stimulation (oscillatory fluid flow), and found that osteoblasts from wild type mice have a stronger response, in terms of ERK1/2 phosphorylation, to both ATP and fluid flow, relative to P2Y2 knockout mice. However, we did not detect any difference in ATP release in response to fluid flow between wild type and P2Y2 knock out osteoblasts. Our findings suggest that P2Y2 receptors play important roles in bone marrow cell differentiation and mineralization as well as in bone cell mechanotransduction, leading to an osteopenic phenotype in P2Y2 knockout mice.
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DOI：
10.1186/1478-811x-11-12
发表时间：
2013-02-17
期刊：
Cell communication and signaling : CCS
影响因子：
--
作者：
Glaser T;Resende RR;Ulrich H
通讯作者：
Ulrich H
影响因子：
6.2
作者：
Wadhwa, S;Godwin, SL;Pilbeam, CC
通讯作者：
Pilbeam, CC
影响因子：
5.6
作者：
Xing, Yanghui;Gu, Yan;Xu, Li-Chong;Siedlecki, Christopher A.;Donahue, Henry J.;You, Jun
通讯作者：
You, Jun
影响因子：
4
作者：
Grol, Matthew W.;Pereverzev, Alexey;Dixon, S. Jeffrey
通讯作者：
Dixon, S. Jeffrey
影响因子：
6.2
作者：
Jorgensen, NR;Henriksen, Z;Steinberg, TH
通讯作者：
Steinberg, TH