Development of an osteoblast cell culture system for functional characterization and comparative analyses of mouse models with bone phenotypes and systemic investigation of an Osteogenesis imperfecta disease model.
München, Technische Universität München, Fakultät Wissenschaftszentrum Weihenstephan, Diss., 2009, 138 S.
1. In vitro analysis of osteoblasts. A comprehensive cell culture system for primary calvarial osteoblasts has been established for in vitro analysis of bone diseases. The system allows to assess general properties of cell growth and to investigate bone specific parameters at the functional-, protein- and RNA-level. The cultivation of the cells independently from systemic influences enables us to find out whether direct alterations of the bone cells (primary effect) or systemic influences (secondary effect) are responsible for a bone disease. 2. Systemic investigation of an Osteogenesis imperfecta (OI) disease model. Cardiovascular and pulmonary diseases are the main causes of death in OI, whereas the pathological alterations in heart and lung are considered as secondary effects caused by the bone disorder. In depth analysis of an OI mouse model provide first time evidence that the collagen alterations in the heart ECM represent the primary cause of the OI lethality and a vicious cycle of heart dysfunction, pulmonary hypertension and hypoxia provokes early death - independent from the bone phenotype.