Spondyloarthritis (SpA) and rheumatoid arthritis (RA) are chronic immune-mediated inflammatory diseases, primarily affecting joints and potentially causing irreversible damage and disability if left untreated. These diseases seem to home more to certain joints than others and, as previously uncovered by our lab, mechanical loading-induced inflammation appeared to be a major cause of this site-specificity. Herein, mechanical load initiates joint inflammation and influences the interplay between myeloid cells and synovial fibroblasts. Fibroblasts are thought to act as primary sensors of mechanical stress and to stimulate an inflammatory cascade and the recruitment and activation of myeloid cells. In this context, MONARCH proposes a proof-of-concept study to primarily investigate the mechanical loading-induced monocyte signature. The observation of the effects of mechanical load across the entire monocytic spectrum will allow us to identify mechano-sensitive pathways that are relevant to arthritis pathogenesis and may be used as therapeutic targets. MONARCH will utilize these pathways to develop monocyte-targeted nanomedicines to tackle the vicious circle between fibroblast and myeloid cell crosstalk underlying mechano-inflammation. Through a translational approach, we aim to develop novel anti-inflammatory therapies for arthritic diseases using a nanomedicine-based drug-delivery system.