Modulation of the canonical Wnt signaling pathway in bone and cartilage

In view of the complex roles of the canonical Wnt signaling during skeletal devel-opment and disease, it is important to accurately distinguish the specific roles of this signaling cascade at specific time windows during embryogenesis as well as postnatally in the maintenance of the skeleton. Moreover, a proper understanding of these multi-faceted roles will ultimately aid us in identifying new therapeutic targets for the treat-ment of growth disorders, osteoporosis and osteoarthritis. Most of the animal models that furnish our knowledge of the effects of canonical Wnt signaling during skeletal development and maintenance use the forced expression of a stabilized and thereby oncogenic _-catenin. The roles of intracellular _-catenin regulators and thereby of wild type _-catenin levels during skeletogenesis, bone mass accrual or AC maintenance are largely unknown. The research described in this thesis aimed at describing the role of two major intracellular regulators of _-catenin, namely Apc and Gsk3_ in regulation of SPC differentiation, bone mass accrual and cartilage maintenance.UBL - phd migration 201