Rheumatoid arthritis and spondyloarthritis are commonly occurring systemic diseases leading to

inflammation and tissue damage in joints. Until recently, there was no clear explanation for this

peculiar disease localization. Our team previously showed in a mouse model of spondyloarthritis

that biomechanical stress may be a critical factor in onset of enthesitis.

In this proposal we will explore the underlying mechanisms by which mechanical strain leads to

joint inflammation with focus on stromal and myeloid cells. As healthy indivuals are also

experiencing biomechanical stress, yet do not develop arthritis, we anticipate that especially the

tissue response in patients with RA or SpA is aberrant.

Our workplan will focus on A20 and S100-DAMPs as central regulators of mechanotransduction

induced arthritis. We will use different in house developed mouse-models that have cell-specific

deletions of A20 to investigate the impact of biomechanical stress on resident and incoming cells.

Overall, this project will shed significant new insights into understanding the role of

mechanotransduction in occurrence of inflammatory arthritis.