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Project TP08





Investigators:
Prof. Dr. Stefan Lossdörfer
Department of Orthodontics
Center of Dento-Maxillo-Facial Medicine
Medical Faculty
University of Bonn


Prof. Dr. Andreas Jäger
Department of Orthodontics
Center of Dento-Maxillo-Facial Medicine
Medical Faculty
University of Bonn



First Funding Period

Role of human periodontal ligament cells and parathyroid hormone in hard tissue repair

Summary
This project deals with the role of periodontal ligament (PDL) cells in periodontal repair following inflammation and trauma and with the involved biological regulatory mechanisms. Analogue to the known anabolic effects of parathyroid hormone (PTH) and of components of the insulin-like growth factor (IGF) system on bone, a potential role of these factors in supporting periodontal repair will be investigated. We hypothesize that an intermittent PTH (1-34) administration will affect the differentiation of human PDL cells and the intracellular signal transduction mainly via protein kinase A. PDL cells will be challenged with PTH(1-34) intermittently in the presence of specific inhibitors to protein kinase A and C. Changes in alkaline phosphatase activity and osteocalcin production will be determined by means of RT PCR and immunoassays. Furthermore, we want to address the question whether a combined treatment regimen comprising an intermittent PTH(1-34) administration plus an exposure of the cells to components of the IGF system would further pronounce the effects on hard tissue repair. In addition to the aims specified, we want to elucidate whether all cells within the mixed population of PDL cells contribute equally to the cellular response or whether it is possible to identify certain subpopulations that the PTH- and/or IGF-induced changes might be attributed to. Finally, the physiological relevance of the in vitro findings will be examined in a rat model using the ?periodontal window wound model? together with histological and histomorphometrical analysis of alveolar bone, PDL and cementum.


Poster



Second Funding Period

Interplay of human periodontal ligament cells and immune cells - age-dependent aspects of the cellular response to intermittent PTH

Summary
This project addresses age-dependent aspects of the immune regulatory function of human periodontal ligament (PDL) cells with special attention directed to the role of an inflammatory microenvironment. Crucial immune regulatory components have been detected in PDL cells and attributed a certain importance in periodontitis. PDL cells have been identified as target cells for regenerative strategies, in part due to their anabolic response to an intermittent parathyroid hormone (PTH) stimulation. The PTH effect on bone metabolism has been linked to T cells since those in turn sensitize stromal cells to PTH. The PDL cell response to intermittent PTH will be investigated in monocultures of PDL cells from donors of different age, macrophages, and T cells with HMGB1, RAGE, TLR-4, CD40, Wnt10b, OPG, and RANKL as target parameters. Co-culture experiments will examine the influence of PDL cells on immune cell chemotaxis and differentiation under variable conditions. Immunocompromised and TLR-4 knockout mice will serve to analyze the physiological relevance. These experimental approaches will elucidate how PDL cells are influenced by immunologic processes or, vice versa, contribute to their regulation, and disclose the role of immune cells for the mediation of the PTH effect on bone remodeling and, conversely, clarify whether immunologic processes can be modified by PTH.