Wnt - FRZB interactions in cartilage.

Osteoarthritis is the most common chronic joint disease. Despite its high incidence and the costs associated with the disease, therapeutic options are limited. The articular cartilage, a tissue that facilitates movement is primarily involved. Drug development has been hindered by a lack of understanding of the way cells communicate with other cells and the environment in the articular cartilage. In this project we will study in detail how Wnt molecules, important regulators of cartilage development and homeostasis, travel from cell to cell within the articular cartilage. We are applying a model developed in developmental biology to a post-natal situation relevant for health and disease. We hypothesize that the interaction between Wnts and their modulators such as FRZB establish concentration gradients that act as signaling centers thereby influencing cell behavior. We propose a step-wise approach using advanced imaging techniques in in vitro models, combined with functional tests in hydrogel-based model tissues and ultimately corroborating this exploratory work in newly developed animal models. This basic research project thereby aims to provide a basis for the development of targeted therapies for osteoarthritis.