Role of hypoxia signalling in cartilage health

Osteoarthritis is a highly prevalent joint disease with a major economic and societal burden. Osteoarthritis involves numerous tissues with an important role in biomechanics. One of these tissues is articular cartilage which provides a smooth surface with low friction to facilitate movement and load distribution to harder bony structures. Cartilage has poor healing capacity and is located in a challenging environment regarding oxygen and nutrient delivery. Cartilage tissue has low cellularity and is composed mainly of type II collagen and proteoglycans that provide unique biomechanical properties for tissue.

It is currently thought that hypoxia-inducible factors (HIF) play a major role in regulating cartilage homeostasis. HIF-1α seems to promote cartilage maintenance through collagen and proteoglycan synthesis. However, there is evidence that HIF-2α would induce chondrocyte hypertrophy and promote osteophyte formation and subchondral bone angiogenesis. Furthermore, it has been proposed that mechanical loading and inflammation could promote HIF-2α signaling.

This project aims to provide further insight into HIF signaling in cartilage. We will evaluate HIF signaling activities in different oxygen tensions and loading levels in cell and tissue culture models to test whether HIF signaling and mechanotransduction are linked. We aim to connect oxygen-sensing activities to cartilage matrix production and degeneration and angiogenic and nerve growth-promoting factors. Finally, in this project, we will test the possible chondroprotective effect of HIF signaling modulators to reduce catabolic changes in cartilage tissue during injurious loading and inflammation.