Wang Hua, Sun Wen, Ma Junqing, Pan Yongchu, Wang Lin, Zhang Wei-Bing
Institute of Stomatology, Jiangsu Key Laboratory of Oral Diseases, Nanjing Medical University, Nanjing, China.
The Research Center for Bone and Stem Cells, Department of Anatomy, Histology and Embryology, Nanjing Medical University, Nanjing, China.
J Biomech. 2015 Feb 5;48(3):432-40. doi: 10.1016/j.jbiomech.2014.12.032. Epub 2014 Dec 18.
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/β-catenin signaling. To investigate the involvement of biglycan and Wnt/β-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/β-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, β-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/β-catenin signaling and Runx2 transcriptional activity. However, silencing osteoblastic biglycan resulted in an attenuated increase in the expression of nuclear active β-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/β-catenin signaling.
已知穿过缝线的机械力可调节缝线骨生成。然而，其潜在机制仍知之甚少。双糖链蛋白聚糖是细胞外基质（ECM）的一种成分，据推测可从ECM中释放并作为信号分子发挥作用。双糖链蛋白聚糖通过Wnt/β-连环蛋白信号传导刺激骨形成。为了研究双糖链蛋白聚糖和Wnt/β-连环蛋白信号传导在缝线扩张骨生成中的作用，我们在体内观察了小鼠腭中缝扩张模型中扩张力诱导的反应，以及在体外观察了双糖链蛋白聚糖缺陷的颅骨成骨细胞中机械应变诱导的Wnt/β-连环蛋白信号传导反应。我们的数据表明，扩张力显著增强了腭中缝边缘的新骨形成。在扩张的腭中缝边缘可见更强的双糖链蛋白聚糖阳性染色。双糖链蛋白聚糖的时空表达与碱性磷酸酶（ALP）和I型胶原蛋白（COL-1）高度一致，这也与整个腭中缝扩张过程中的新骨形成相吻合。双糖链蛋白聚糖、β-连环蛋白以及包括Runx2、ALP和COL-1在内的成骨标志物的蛋白质和mRNA水平均同时升高。此外，机械应变充分诱导了成骨细胞双糖链蛋白聚糖的上调，这与应变诱导的Wnt/β-连环蛋白信号传导增强和Runx2转录活性增强平行。然而，沉默成骨细胞双糖链蛋白聚糖会导致响应机械应变时核活性β-连环蛋白和Runx2表达的增加减弱。我们的数据表明，双糖链蛋白聚糖作为ECM的一种成分，通过激活Wnt/β-连环蛋白信号传导介导缝线扩张骨生成。
