Although various joint injuries result in post-traumatic osteoarthritis (PTOA), differences in chondrocyte response to specific injuries, such as blunt compression or fracture, are unclear. Furthermore, the role of underlying joint inflammation, or synovitis, is often not considered. We investigated how injury mechanisms and underlying synovitis affect chondrocyte gene expression using osteochondral injury models with synovial co-culture. We hypothesized that the state of synovitis as well as the mechanism of biomechanical cartilage injury differentially alter the gene expression of chondrocytes and that these responses are regulated by the pro-inflammatory cytokine interleukin 1 (IL-1). The mechanism of injury and level of synovial inflammation both significantly regulated chondrocyte gene expression and associated pathways, uncovering distinct characteristics of fracture and compression injury mechanisms. Targeting IL-1 following injury reduced the inflammatory response and could have clinical implications. The results from this study show that crosstalk between biomechanics and inflammation in the context of synovitis and cartilage injury mechanism is an important consideration for PTOA.

Posttraumatic osteoarthritis (PTOA) is a subset of osteoarthritis that occurs after joint injury and is associated with degradation of articular cartilage and subchondral bone. As compared with primary osteoarthritis, PTOA occurs in a time window initiated by a traumatic event resulting in damage to layers of joint structure and alterations in joint shape. As techniques in open reduction and internal fixation continue to mature, our success in preventing posttraumatic osteoarthritis has not kept pace. Advances in research in the subchondral bone, inflammatory response, and joint mechanics continue to open our understanding of this posttraumatic process. In addition, there are possibilities emerging as biological agents to therapeutically alter the progression of PTOA.