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，牙根骨质和牙周器官的持续重塑是维持组织强度、防止损伤和固定牙齿的必要条件。在牙周组织中，牙根骨质和牙周韧带是功能组织稳态的关键调节因子。牙根骨质为牙根提供牙周韧带纤维的锚定，牙周韧带本身是组织吸收、重塑过程和机械信号传递的关键调节者。因此，两种组织的平衡串扰对于维持这个复杂系统的稳态是必需的。最近的研究表明，牙周组织的不同结构和细胞类型对机械应力表现出不同的个体反应。人类牙周韧带成纤维细胞（hPDLF）和干细胞在组织重塑和再生方面的细胞因子和生长因子的分泌已经在多项工作中得到了研究。近年来，成水泥细胞对PDL的连接起着至关重要的作用，并成为科学研究的焦点。因此，不同类型的细胞在机械负荷诱导的牙周重塑中的个体作用需要被识别和理解，以便更好地理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策略。在本项目中，我们的目标是填补对牙骨质和牙周如何调节以及组织之间相互作用的认识不足的空白，以确保持续的重塑，在牙周韧带和牙根牙骨质之间提供足够的牙锚定。第一步将是建立患者PDLSC和成水泥细胞的分离和表征。这两种细胞类型将从同一患者中分离出来，以产生稳定的，荧光标记的细胞系，以追踪三维组织工程牙周结构中的细胞命运。下一步，我们的目标是分析PDLSC和成水泥细胞的具体特征，以及这些细胞在生理条件下的相互作用，以及与机械负荷诱导的组织重塑的相互作用，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，我们将在体外验证参与压缩力的关键分子，以一种我们支持牙周骨质串扰的方式，进一步了解牙周重塑、信号传导和调节。预期的研究结果，除了获得牙周骨质组织及其串扰的核心知识外，还显示了在正畸治疗中调节牙周重塑和减少牙根吸收的可能治疗方面的观点。

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.