The Role of Synovium and Synovial Macrophages in Experimental Post-Traumatic Knee Osteoarthritis

In osteoarthritis (OA), synovitis is associated with symptom severity. As synovium secretes both catabolic and anabolic factors into the joint, the impact of synovitis in OA remains unclear. We developed a novel co-culture system using tissues from an established rat model of post-traumatic knee OA (PTOA) to study signaling between synovium and chondrocytes. We found that synovium from early stage but not later stage PTOA joints caused an overall protective effect in chondrocytes. We then selectively treated synovial macrophages with liposomal drugs causing depletion, STAT1 inhibition, or STAT6 inhibition in early PTOA joints. We found cartilage damage in vivo was not affected, but chondrocyte responses to treated synovium in vitro indicate that STAT1 inhibition could be protective, while STAT6 inhibition is potentially pro-inflammatory. Thus, we demonstrate that synovial signals affect chondrocyte physiology in the OA knee joint and that targeting synovial macrophages as a potential therapeutic strategy warrants further investigation.