Biglycan mediates suture expansion osteogenesis via potentiation of Wnt/β-catenin signaling
Biglycan mediates suture expansion osteogenesis via potentiation of Wnt/β-catenin signaling
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DOI：
10.1016/j.jbiomech.2014.12.032
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发表时间：
2015-02-05
影响因子：
2.4
通讯作者：
Zhang, Wei-Bing
中科院分区：
文献类型：
--
作者：
Wang, Hua;Sun, Wen;Zhang, Wei-Bing
已知穿过缝合线的机械力可调节缝合线成骨。然而，潜在的机制仍然知之甚少。Biglycan是细胞外基质（ECM）的一种成分，被认为可以从ECM中释放出来，并发挥信号分子的作用。Biglycan通过Wnt/ β -连环蛋白信号传导刺激骨形成。为了研究biglycan和Wnt/ β -catenin信号在缝线扩张成骨中的作用，我们在小鼠中腭缝线扩张模型中观察了扩张力诱导的反应，在体外观察了缺乏biglycan的颅骨成骨细胞中Wnt/ β -catenin信号诱导的机械应变反应。我们的数据显示，扩张力显著促进了中腭缝合线边缘的新骨形成。在扩张的中腭缝合线边缘可见较强的biglycan阳性染色。biglycan的时空表达与ALP和COL-1高度一致，也与整个中腭缝线扩张过程中新骨的形成相吻合。biglycan、β -连环蛋白、Runx2、ALP、COL-1等成骨标志物的蛋白和mRNA水平均升高。此外，机械应变充分诱导了成骨细胞biglycan的上调，这与菌株诱导的Wnt/ β -catenin信号通路和Runx2转录活性的增强是平行的。然而，沉默成骨细胞biglycan导致核活性β -catenin和Runx2在机械应变下的表达增加减弱。我们的数据表明，biglycan作为ECM的一个组成部分，通过激活Wnt/ β -连环蛋白信号通路介导缝线扩张成骨。(C) 2014 Elsevier Ltd.版权所有。
Mechanical force across sutures is known to modulate suture osteogenesis. However, the underlying mechanisms still remain poorly understood. Biglycan is a component of extracellular matrix (ECM) that is postulated to release from ECM and function as a signaling molecule. Biglycan stimulates the bone formation through Wnt/beta-catenin signaling. To investigate the involvement of biglycan and Wnt/beta-catenin signaling in suture expansion osteogenesis, we observed the expansion force-induced response in mouse midpalatal suture expansion model in vivo, and the mechanical strain-induced response of Wnt/beta-catenin signaling in biglycan-deficient calvarial osteoblasts in vitro. Our data showed that expansion force significantly enhanced new bone formation at the edge of midpalatal sutures. Stronger biglycan positive staining was visible at the edge of expanding midpalatal sutures. The spatio-temporal expression of biglycan was highly consistent with ALP and COL-1, which also coincided with new bone formation throughout the midpalatal suture expansion process. Both protein and mRNA levels of biglycan, beta-catenin, and osteogenic markers including Runx2, ALP and COL-1 were increased together. In addition, mechanical strain sufficiently induced upregulation of osteoblastic biglycan, which was paralleled with the strain-induced potentiation of Wnt/beta-catenin signaling and Runx2 transcriptional activity. However, silencing osteoblastic biglycan resulted in an attenuated increase in the expression of nuclear active beta-catenin and Runx2 in response to mechanical strain. Our data demonstrated that biglycan as a component of ECM mediates suture expansion osteogenesis through the activation of Wnt/beta-catenin signaling. (C) 2014 Elsevier Ltd. All rights reserved.