Synovial fibroblasts assume distinct functional identities and secrete R-spondin 2 to drive osteoarthritis

Synovium is acutely affected following joint trauma and contributes to post-traumatic osteoarthritis (PTOA) progression. Little is known about discrete cell types and molecular mechanisms in PTOA synovium. We aimed to describe synovial cell populations and their dynamics in PTOA. Single-cell RNA-seq profiling of synovium revealed fibroblasts (comprised of various functional subsets), macrophages, endothelial cells and pericytes to be the predominanent synovial cell types, along with rarer populations including T cells, Schwann cells and mast cells. Cell types undergo profound changes in abundance and gene expression following joint injury. Overall design: Single-cell RNA-sequencing of murine knee synovium. Mice were subjected to non-invasive anterior cruciate ligament rupture (ACLR) to induce post-traumatic osteoarthritis. Synovium were harvested from one male and one female mouse (pooled) for the following three conditions: Sham (no injury), 7d post-ACLR, 28d post-ACLR. Two biological replicates were performed for each condition for a total of six samples (with each sample comprised of one male, one female).