Masella Richard S, Meister Malcolm
Department of Orthodontics, College of Dental Medicine, Nova Southeastern University, Fort Lauderdale, FL 33328, USA.
Am J Orthod Dentofacial Orthop. 2006 Apr;129(4):458-68. doi: 10.1016/j.ajodo.2005.12.013.
Adaptive biochemical response to applied orthodontic force is a highly sophisticated process. Many layers of networked reactions occur in and around periodontal ligament and alveolar bone cells that change mechanical force into molecular events (signal transduction) and orthodontic tooth movement (OTM). Osteoblasts and osteoclasts are sensitive environment-to-genome-to-environment communicators, capable of restoring system homeostasis disturbed by orthodontic mechanics. Five micro-environments are altered by orthodontic force: extracellular matrix, cell membrane, cytoskeleton, nuclear protein matrix, and genome. Gene activation (or suppression) is the point at which input becomes output, and further changes occur in all 5 environments. Hundreds of genes and thousands of proteins participate in OTM. Gene-directed protein synthesis, modification, and integration form the essence of all life processes, including OTM. Bone adaptation to orthodontic force depends on normal osteoblast and osteoclast genes that correctly express needed proteins at the right times and places. Cell membrane receptor-ligand docking is an important initiator of signal transduction and a discovery target for new bone-enhancing drugs. Despite progress in identification of regulatory molecules, the genetic mechanism of "orchestrated synthesis" between different cells, tissues, and systems remains largely unknown. Interpatient variation in mechanobiological response is most likely due to differences in periodontal ligament and bone cell populations, genomes, and protein expression patterns. Discovery of mutations in OTM-associated genes of orthodontic patients, including those regulating osteoclast bone-matrix acidification, chloride channel function, and osteoblast-derived mineral and protein matrices, will permit gene therapy to restore normal matrix and protein synthesis and function. Achieving selectivity in targeting abnormal genes, cells, and tissues is a major obstacle to safe and effective clinical application of gene engineering and stem-cell mediated tissue growth. Orthodontic treatment is likely to evolve into a combination of mechanics and molecular-genetic-cellular interventions: a change from shotgun to tightly focused communication with OTM cells.
对正畸力的适应性生化反应是一个高度复杂的过程。在牙周韧带和牙槽骨细胞及其周围会发生许多层相互关联的反应，这些反应将机械力转化为分子事件（信号转导）和正畸牙齿移动（OTM）。成骨细胞和破骨细胞是环境与基因组之间以及基因组与环境之间敏感的通讯者，能够恢复因正畸力学而被扰乱的系统稳态。正畸力会改变五个微环境：细胞外基质、细胞膜、细胞骨架、核蛋白基质和基因组。基因激活（或抑制）是输入转化为输出的关键点，并且在所有五个环境中都会进一步发生变化。数百个基因和数千种蛋白质参与正畸牙齿移动。基因指导的蛋白质合成、修饰和整合构成了包括正畸牙齿移动在内的所有生命过程的本质。骨骼对正畸力的适应取决于正常的成骨细胞和破骨细胞基因，这些基因能在正确的时间和地点正确表达所需的蛋白质。细胞膜受体 - 配体对接是信号转导的重要启动因素，也是新型骨增强药物的发现靶点。尽管在鉴定调控分子方面取得了进展，但不同细胞、组织和系统之间“协调合成”的遗传机制仍 largely 未知。患者间机械生物学反应的差异很可能是由于牙周韧带和骨细胞群体、基因组以及蛋白质表达模式存在差异。在正畸患者的正畸牙齿移动相关基因中发现突变，包括那些调节破骨细胞骨基质酸化、氯离子通道功能以及成骨细胞衍生的矿物质和蛋白质基质的基因，将使基因治疗能够恢复正常的基质和蛋白质合成及功能。在靶向异常基因、细胞和组织时实现选择性是基因工程和干细胞介导的组织生长安全有效临床应用的主要障碍。正畸治疗可能会演变为力学与分子 - 遗传 - 细胞干预的结合：从广泛的方法转变为与正畸牙齿移动细胞进行精准聚焦的通讯。
