Synovial Fluid Mitochondrial DNA as a Biomarker of Articular Cartilage Injury. Seewald LA, Sabino IG, Bohner A, Delco ML. Cornell University, College of Veterinary Medicine, Ithaca, NY.
Mitochondrial dysfunction is one of the earliest responses of chondrocytes to cartilage injury, representing an important link between acute articular trauma, ongoing inflammation, and progression to post-traumatic osteoarthritis (PTOA). We recently found that, in vitro, chondrocytes release mitochondrial DNA (mtDNA) as an acute-phase response to mitochondrial stress; however, mtDNA has not been evaluated as a marker of joint injury. Thus, the goals of this study were to investigate if synovial fluid (SF) mtDNA is a clinically useful marker of articular injury, and if mitoprotective therapy with SS-31 prevents mtDNA release. Samples from ex vivo and in vivo experimental cartilage injury models (cartilage-conditioned media and SF, respectively) were analyzed, as was equine SF from clinical cases of carpal fracture (n = 19), and talocrural joint disease, including osteochondritis dissecans (n = 26), fracture (n = 3), and septic arthritis (n = 3). Taqman qPCR was used to quantify mtDNA and nuclear DNA concentrations. Both ex vivo and in vivo models of cartilage impact revealed elevations in extracellular mtDNA, which were mitigated by mitoprotective therapy. Joints with naturally occurring intra-articular fracture had markedly increased SF mtDNA and nDNA compared to normal joints. Arthroscopic scoring revealed a strong positive correlation between cartilage lesion depth and SF mtDNA (r = 0.80, P = 0.0001). These data suggest SF mtDNA may represent a sensitive marker of articular injury, prior to detectable changes on diagnostic imaging. In addition to aiding in the diagnosis of subclinical cartilage injury, mtDNA may prove useful in case selection for early intervention to prevent progressive joint injury, fracture, and/or PTOA.