Overeenkomsten en verschillen in de bestuursrechtelijke handhaving bij het bouw- en woningtoezicht van het huidige stelsel in Nederland en Nordrhein-Westfalen

in deze scriptie wordt verslag gedaan van een onderzoek naar de overeenkomsten en verschillen in de bestuursrechtelijke handhaving van het bouw- en woningtoezicht van het huidige stelsel in Nederland en Nordrhein-Westfalen

Human Osteoblast Differentiation and Bone Formation: Growth Factors, Hormones and Regulatory Networks

Osteoporosis is the most common bone disease and is characterized by low bone mass, micro architectural deterioration and decreased bone quality resulting in increased risk of fractures. Osteoblasts, the bone forming cells, play a crucial role in the regulation of bone mass and bone quality. Osteoblasts are of mesenchymal origin and undergo a complex differentiation process regulated by many endocrine and autocrine factors. In order to develop novel bone anabolic drugs, more knowledge concerning osteoblast biology is required. In this thesis we investigated the processes of human osteoblast differentiation and matrix mineralization. Human osteoblast-based models of bone formation were used in which the role of glucocorticoids (GCs), 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), the Wnt signaling pathway and the activin A-follistatin system were studied

Calcifying vascular smooth muscle cells and osteoblasts: Independent cell types exhibiting extracellular matrix and biomineralization-related mimicries

Background: Ectopic vascular calcifications represent a major clinical problem associated with cardiovascular disease and mortality. However, the mechanisms underlying pathological vascular calcifications are largely unknown hampering the development of therapies to tackle this life threatening medical condition. Results: In order to gain insight into the genes and mechanisms driving this pathological calcification process we analyzed the transcriptional profile of calcifying vascular smooth muscle cells (C-VSMCs). These profiles were compared to differentiating osteoblasts, cells that constitute their physiological calcification counterparts in the body. Overall the transcriptional program of C-VSMC and osteoblasts did not overlap. Several genes, some of them relevant for bone formation, were distinctly modulated by C-VSMCs which did not necessarily lose their smooth muscle cell markers while calcifying. Bioinformatics gene clustering and correlation analysis disclosed limited bone-related mechanisms being shared by two cell types. Extracellular matrix (ECM) and biomineralization genes represented common denominators between pathological vascular and physiological bone calcifications. These genes constitute the strongest link between these cells and represent potential drivers for their shared end-point phenotype. Conclusions: The analyses support the hypothesis that VSMC trans-differentiate into C-VSMCs keeping their own identity while using mechanisms that osteoblasts use to mineralize. The data provide novel insights into groups of genes and biological processes shared in MSC and VSMC osteogenic differentiation. The distinct gene regulation between C-VSMC and osteoblasts might hold clues to find cell-specific pathway modulations, opening the possibility to tackle undesired vascular calcifications without disturbing physiologic bone formation and vice versa