Early detection of orthopaedic conditions following a mechanical injury could potentially prevent the development of posttraumatic osteoarthritis (PTOA). Mitochondrial dysfunction is an acute response of chondrocytes to mechanical injury, which eventually leads to the development of PTOA. The use of a diagnostic test, sensitive enough to identify mitochondrial dysfunction in patients, would therefore contribute to the preservation of mitochondrial structure and function (aka mitoprotection) and potentially prevent PTOA progression. A manuscript published recently by Seewald et al. in Osteoarthritis and Cartilage, went on to evaluate whether mitochondrial dysfunction could serve as an indicator of cartilage damage, for early detection of posttraumatic osteoarthritis.
The authors used a series of different translational models of PTOA, all approved by the Cornell University’s Institutional Animal Care and Use Committee. An explant model of articular injury was used to evaluate mitochondrial DNA (mtDNA) release following mechanical overload, an equine model of impact-induced articular injury was used to evaluate mtDNA content in synovial fluid and finally, equine naturally occurring intra-articular fracture cases were scored for lesions of the cartilage, subchondral bone, and synovium.
Findings showed that a) chondrocytes released mtDNA following inflammatory and mechanical cellular stress in vitro, b) mtDNA was increased in equine synovial fluid following experimental and naturally occurring injury, and c) there was a strong correlation between the degree of cartilage damage and mtDNA concentration. Finally, experiments proved that impact-induced mtDNA release was mitigated by treatment with the mitoprotective peptide SS-31 (elamipretide), which belongs to a class of mitoprotective agents that have been shown to repair cristae structure and restore mitochondrial function.
This work was the first to investigate mtDNA as a potential biomarker in PTOA. Authors concluded that joint injury causes changes in synovial fluid mtDNA and these correlate with the severity of cartilage damage. Moreover, they pointed out that mitoprotection mitigates increases in synovial fluid mtDNA and suggested that mtDNA release may reflect mitochondrial dysfunction. Finally, they acknowledged the need to study synovial fluid mtDNA changes in human clinical cohorts in order to determine its diagnostic and prognostic utility for PTOA.