Fig. 1. Study design leveraging multi-omics profiling from osteoarthritis patient tissues.

We examined the molecular characteristics of osteoarthritis by profiling mRNA and proteins from low-grade cartilage, high-grade cartilage and synovium tissue of over 100 patients undergoing total joint replacement for osteoarthritis, and combining these data with patient genotypes. We identified genetic variants influencing mRNA or protein levels, several of which co-localise with genetic risk variants for osteoarthritis. We also identified molecular markers of cartilage degeneration, creating a gene expression profile of degeneration, and shortlisting existing drugs or compounds that reverse this profile in cell experiments.