Understanding the PDL cell / cementum interphase, their interplay under mechanical stress and periodontal remodeling to provide a basis for periodontal-cementum research

临床证据表明，在生理和治疗条件下，牙根牙骨质和牙周组织的持续重塑是保持组织强度、防止损伤和确保牙齿支抗所必需的。在牙齿周围组织中，牙根牙骨质和牙周韧带是功能性组织稳态的关键调节器。虽然根牙骨质提供牙周膜纤维到牙根的锚定，但牙周膜本身是组织吸收、重塑过程和机械信号传递的关键调节器。因此，两种组织的平衡串扰对于维持该复杂系统的稳态是强制性的。近年来的研究表明，牙周组织的不同结构和细胞类型对机械应力有不同的反应。人牙周膜成纤维细胞（hPDLF）和干细胞已经在多项关于分泌细胞因子、生长因子在组织重塑和再生方面的工作中进行了研究。近年来，成牙骨质细胞在牙周膜连接中发挥着重要作用，成为科学研究的热点。因此，不同类型的细胞参与机械负荷诱导的牙周重塑的个别作用需要被识别和理解，以便更好地了解牙骨质和牙周组织的功能串扰。因此，有必要制定创新的研究战略。在目前的项目中，我们的目标是关闭之间的差距差距缺乏知识，如何牙骨质和牙周的调节和组织相互作用，以确保持续重塑提供足够的牙齿锚定牙周膜和牙根牙骨质。第一步将是从患者中分离和鉴定PDLSC和成牙骨质细胞。两种细胞类型将从同一患者中分离，以产生稳定的荧光标记细胞系，从而在三维组织工程牙周构建体中追踪细胞命运。在下一步中，我们的目标是分析PDLSC和成牙骨质细胞的特定特征以及这些细胞在生理条件下以及与机械负荷诱导的重塑之间的相互作用，以解决组织重塑的中心调节因素。在从我们的活性激酶谱中获得新知识后的最后一步中，我们将以支持牙周牙骨质串扰的方式验证参与压缩力的体外关键分子，以进一步获得牙周重塑，信号传导和调节的内部信息。预期的研究结果，除了获得一个中央知识的牙周牙骨质组织和它的串扰，还显示了有关可能的治疗方面的观点，以调节牙周重塑和减少牙根吸收的正畸治疗。

Clinical evidence indicates that a continuous remodeling of the tooth root cementum and the periodontal apparatus in physiological and therapeutic conditions is required to maintain tissue strength, to prevent from damage, and to secure teeth anchorage. Within the tooth surrounding tissues, tooth root cementum and the periodontal ligament are the key regulators of a functional tissue homeostasis. While the root cementum supplies the anchorage of periodontal ligament fibers to the tooth root, the periodontal ligament itself is the key regulator of tissue resorption, remodeling process, and mechanical signal transmission. Thus, a balanced crosstalk of both tissues is mandatory for maintaining a homeostasis of this complex system. There is recent knowledge that different structures and cell types of the periodontium show distinct and individual respond to mechanical stress. Human periodontal ligament fibroblasts (hPDLF) and stem cells have already been investigated in multiple works concerning secretion of cytokines, growth factors in terms of tissue remodeling and regeneration. Recently, cementoblasts are of central importance for PDL connection and shift into the focus of science. Thus, the individual role of different cell types involved in mechanical loading-induced periodontal remodeling needs to be identified and understood in order to gain a better understanding into the functional crosstalk of cementum and periodontal tissues. For this reason it is necessary to develop innovative research strategies. In the present project, we aim to close the gap between the lack of knowledge how cementum and periodontal is regulated and tissues interact with each other in order to ensure continuous remodeling providing sufficient tooth anchorage between periodontal ligament and tooth root cementum. The first step will be the establishment of the isolation and characterization of PDLSC and cementoblast cells from patients. Both cell types will be isolated from the same patient to generate stable, fluorescently labeled cell lines to trace cell fate in three-dimensional tissue engineered periodontal constructs. In the next step we aim to analyze specific characteristics of the PDLSC and cementoblasts and the interaction between these cells under physiological conditions as well as with mechanical loading induced remodeling addressing central regulatory factors for tissue remodeling. In the final step after gaining new knowledge from our activity kinase profile, we will validate in vitro key molecules involved in compression force in a way that we support periodontal cementum crosstalk to gain further insides of periodontal remodeling, signaling and regulation. The expected findings should, in addition to gaining a central knowledge of the periodontal cementum tissues and its crosstalk, also show perspectives regarding possible therapeutic aspects to regulate periodontal remodeling and to reduce root resorptions in orthodontic therapies.