Planar cell polarity aligns osteoblast division in response to substrate strain.
Planar cell polarity aligns osteoblast division in response to substrate strain.
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DOI：
10.1002/jbmr.2377
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发表时间：
2015-03
影响因子：
6.2
通讯作者：
Price, Joanna S.
中科院分区：
文献类型：
--
作者：
Galea, Gabriel L.;Meakin, Lee B.;Savery, Dawn;Taipaleenmaki, Hanna;Delisser, Peter;Stein, Gary S.;Copp, Andrew J.;van Wijnen, Andre J.;Lanyon, Lance E.;Price, Joanna S.
骨骼暴露于动态应变下会增加成骨细胞的分裂速度，还会影响它们产生的骨组织的细胞和分子结构的定向组织。在这里，我们报告短暂暴露于动态基质应变（足以快速刺激细胞分裂）会影响成骨细胞分裂的方向。对菌株的最初增殖反应涉及典型的 Wnt 信号传导，并且可以被硬化蛋白阻断。然而，与应变相关的细胞分裂方向受到非规范 Wnt/平面细胞极性 (PCP) 途径的独立影响。阻断 Rho 相关卷曲激酶 (ROCK)（PCP 通路的一个组成部分）可防止成骨细胞样 Saos-2 细胞中与应变相关的分裂方向。小鼠成骨细胞中核心 PCP 成分 van Gogh-like 2 (Vangl2) 的杂合环尾突变会损害响应应变的分裂方向。通过 µCT 和扫描电子显微镜对 Vangl2 环尾杂合小鼠的骨骼进行检查，发现骨结构发生了改变，骨形成表面也变得杂乱无章。因此，除了 PCP 参与骨骼形态发生过程中对发育线索的反应中广泛接受的作用外，我们的数据表明，该途径还在出生后发挥作用，与典型的 Wnt 信号传导并行，将生物力学线索转变成骨骼适应性反应。这两条途径同时且独立的作用似乎会影响成骨细胞分裂的速率和方向，从而微调骨结构以满足功能负荷的结构需求。 © 2014 作者。 《Journal of Bone and Mineral Research》由 Wiley periodicals, Inc. 代表美国骨与矿物质研究学会出版。
Exposure of bone to dynamic strain increases the rate of division of osteoblasts and also influences the directional organization of the cellular and molecular structure of the bone tissue that they produce. Here, we report that brief exposure to dynamic substrate strain (sufficient to rapidly stimulate cell division) influences the orientation of osteoblastic cell division. The initial proliferative response to strain involves canonical Wnt signaling and can be blocked by sclerostin. However, the strain-related orientation of cell division is independently influenced through the noncanonical Wnt/planar cell polarity (PCP) pathway. Blockade of Rho-associated coiled kinase (ROCK), a component of the PCP pathway, prevents strain-related orientation of division in osteoblast-like Saos-2 cells. Heterozygous loop-tail mutation of the core PCP component van Gogh-like 2 (Vangl2) in mouse osteoblasts impairs the orientation of division in response to strain. Examination of bones from Vangl2 loop-tail heterozygous mice by µCT and scanning electron microscopy reveals altered bone architecture and disorganized bone-forming surfaces. Hence, in addition to the well-accepted role of PCP involvement in response to developmental cues during skeletal morphogenesis, our data reveal that this pathway also acts postnatally, in parallel with canonical Wnt signaling, to transduce biomechanical cues into skeletal adaptive responses. The simultaneous and independent actions of these two pathways appear to influence both the rate and orientation of osteoblast division, thus fine-tuning bone architecture to meet the structural demands of functional loading. © 2014 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals, Inc. on behalf of the American Society for Bone and Mineral Research.
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DOI：
10.1242/dev.091173
发表时间：
2013-07
期刊：
Development (Cambridge, England)
影响因子：
--
作者：
Escobedo N;Contreras O;Muñoz R;Farías M;Carrasco H;Hill C;Tran U;Pryor SE;Wessely O;Copp AJ;Larraín J
通讯作者：
Larraín J
影响因子：
4.1
作者：
Ding, M;Hvid, I
通讯作者：
Hvid, I
影响因子：
3.7
作者：
Bhadriraju, Kiran;Yang, Michael;Chen, Christopher S.
通讯作者：
Chen, Christopher S.
影响因子：
--
作者：
FROST, HM
通讯作者：
FROST, HM
影响因子：
4.8
作者：
Armstrong, Victoria J.;Muzylak, Mariusz;Lanyon, Lance E.
通讯作者：
Lanyon, Lance E.