Mechanical regulation of synoviocyte response to pro-inflammatory cytokines and development of a synovium-cartilage chip
Physiological mechanical loading is known to be important in maintaining healthy cartilage whilst high magnitudes and strain rates may lead to cartilage degradation. The overall aim of this study is to develop an organ-on-a-chip model comprising both cartilage and synovium cells and to use this to examine the interaction between the two cell types and their response to physiological and pathological loading and the pro-inflammatory cytokine, IL-1β. This work will also involve examining the role of the primary cilium, a specialist cellular organelle important in mechanosignalling and regulation of tissue health and disease.
This project will improve understanding of arthritis and aid the development of novel therapeutics for treatment of this painful and debilitating condition.
The specific aims of the project are as follows:
- Identify the effect of physiological and pathological mechanical loading of synoviocytes on the response to the pro-inflammatory cytokine, IL-1β.
- Determine how mechanical loading of synovium regulates chondrocyte behavior and response to IL-1β.
- Determine the role of primary cilia in the response of synoviocytes to mechanical loading and the cross-talk with chondrocytes.
- Develop a chondrocyte-synoviocyte co-culture organ-on-a-chip model.
- Use the for organ-on-a-chip model to test the anti-inflammatory effect of known regulators of primary cilia expression in order to identify potential new drug candidates for treatment of inflammatory arthritis.