Unraveling a new molecular link between Wnt signaling and IGF1 in the chondrocyte and its therapeutic implications for osteoarthritis

Osteoarthritis is the most common chronic joint disease worldwide, in
which progressive joint damage leads to pain and disability.
Currently, no therapeutic strategies are available that revert or stop
the progression of the disease. In osteoarthritis, cartilage cells often
develop abnormal differentiation towards hypertrophy, which
contributes to joint destruction. These changes are associated with
excessive activation of Wnt signaling. However, how Wnt signaling
triggers hypertrophic differentiation is largely unknown. We have
preliminary evidence that excessive Wnt increases local production
of insulin growth factor-1 (IGF1), a key player in the hypertrophy
process in bone development. Here, we aim to find out how Wnt
increases IGF1 and whether the downstream effects of this
interaction impact osteoarthritis. We will also explore therapeutic
implications for the disease. We will use a translational research
approach including state-of-the-art technologies in the analysis of
patient-derived cells and explants, combined with different mouse
models of osteoarthritis. An important tool will be a new genetic
mouse model with cartilage-specific inducible loss of the Igf1 gene. A
successful project will lead to the identification of molecular events
that trigger key disease-associated changes in cartilage, and may
contribute to opportunities for osteoarthritis therapy.