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.