Department of Oral Cell Biology, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and VU University Amsterdam , Amsterdam, The Netherlands .
Tissue Eng Part C Methods. 2009 Dec;15(4):561-70. doi: 10.1089/ten.TEC.2008.0336.
In this study we present a new three-dimensional (3D) model to study effects of mechanical loading on tendon/ligament formation in vitro. The model mimics a functional periodontal ligament (PDL), which anchors dental roots to the jaw bone and transfers the axial load of mastication to the jaw bone. A collagen gel containing human PDL fibroblasts was seeded in a PDL space between an artificial root and bone surface. The effects of 3-day loading on the fibroblasts were studied in vitro by axial and intermittent displacement of the root to which the gel was attached. Cell responses were recorded by measuring expression of three sets of genes: (i) cyclooxygenase 1 and 2 (COX-1, COX-2) producing prostaglandins (signaling molecules); (ii) Runx2, a transcription factor for the osteogenic lineage; and (iii) the extracellular matrix proteins osteopontin, dentin matrix protein 1, and collagen type I (COL1). Loading for 3 days resulted in magnitude-dependent changes in the expression of COX-2 and COL1. A low loading magnitude significantly decreased COX-2 expression, an intermediate magnitude increased its expression, while a high magnitude increased COL1 expression. We concluded that the 3D loading model provides a useful, well-controlled method to examine ligament fibroblast responses to mechanical loading. The model may serve to explore the application of mechanical loading as an anabolic factor for ligament reconstruction.
在这项研究中，我们提出了一种新的三维（3D）模型，用于研究机械加载对体外肌腱/韧带形成的影响。该模型模拟了功能性牙周韧带（PDL），它将牙根固定在颌骨上，并将咀嚼的轴向力传递到颌骨上。将含有人牙周膜成纤维细胞的胶原凝胶接种在人工牙根和骨表面之间的牙周间隙中。通过对附着凝胶的牙根进行轴向和间歇位移，在体外研究了 3 天加载对成纤维细胞的影响。通过测量三组基因的表达来记录细胞反应：（i）产生前列腺素的环氧化酶 1 和 2（COX-1、COX-2）（信号分子）；（ii）Runx2，成骨谱系的转录因子；和（iii）细胞外基质蛋白骨桥蛋白、牙本质基质蛋白 1 和胶原 I（COL1）。3 天的加载导致 COX-2 和 COL1 的表达与幅度相关的变化。低加载幅度显著降低 COX-2 的表达，中等幅度增加其表达，而高幅度增加 COL1 的表达。我们得出结论，3D 加载模型为研究韧带成纤维细胞对机械加载的反应提供了一种有用且可控的方法。该模型可用于探索机械加载作为韧带重建的合成代谢因子的应用。
