Synovial fluid mitochondrial DNA concentration reflects the degree of cartilage damage after naturally occurring articular injury

Seewald LA, Sabino IG, Montney KL, Delco ML · Osteoarthritis and Cartilage

The in-vivo arm is a re-analysis of banked synovial fluid from an equine impact-injury model. Intra-articular SS-31 given an hour after injury lowered synovial-fluid mitochondrial DNA against untreated joints at days 14 and 28 and lowered cell death at every timepoint; the mtDNA:nDNA ratio did not differ between treated and untreated joints, and across the model as a whole mtDNA rose above pre-injury baseline only at day 7. In cultured chondrocytes SS-31 raised maximum oxygen consumption rate and spare respiratory capacity. Across 19 horses with naturally occurring carpal fracture, mean cartilage lesion depth correlated with synovial mtDNA at r=0.80 (p=0.0001), the strongest of the component criteria, and the total arthroscopic lesion score at r=0.76 (p=0.0004).

Population

12 adult horses with arthroscopically created talar cartilage impact injuries, plus explant, culture, and naturally occurring injury cohorts

Intervention

Intra-articular SS-31 (elamipretide, 1 µM) injected into both joints 1 hour after injury, surgeon blinded

Comparator

Intra-articular saline

Limitations

The in-vivo arm randomised six horses per group by coin toss and analysed by joint: both joints of one SS-31 horse were excluded for abnormal conformation, leaving ten treated joints against twelve, and one control horse was euthanised at five weeks for an unrelated emergency with its sample assigned to the 42-day timepoint. The endpoints are a biomarker and cell death rather than cartilage structure, function or the development of osteoarthritis, and the authors say synovial-fluid mtDNA cannot be treated as specific to cartilage because synovium, subchondral bone and infiltrating immune cells are likely to contribute. The soft-tissue-swelling cut-off was not set in advance. Funded by NIH NIAMS and the Harry M. Zweig Fund for Equine Research, with no competing interests declared.