College of Veterinary Medicine, Cornell University, Ithaca, NY, USA.
Osteoarthritis Cartilage. 2023 Aug;31(8):1056-1065. doi: 10.1016/j.joca.2023.03.013. Epub 2023 Apr 6.
To evaluate mitochondrial DNA (mtDNA) release from injured chondrocytes and investigate the utility of synovial fluid mtDNA concentration in early detection of posttraumatic osteoarthritis.
We measured mtDNA release using four models of osteoarthritis: in vitro interleukin-1β stimulation of cultured equine chondrocytes, ex vivo mechanical impact of bovine cartilage explants, in vivo mechanical impact of equine articular cartilage, and naturally occurring equine intraarticular fracture. In our in vivo model, one group was treated with an intraarticular injection of the mitoprotective peptide SS-31 following cartilage injury. mtDNA content was quantified using qPCR. For naturally occurring cases of joint injury, clinical data (radiographs, arthroscopic video footage) were scored for criteria associated with degenerative joint disease.
Chondrocytes released mtDNA in the acute time frame following inflammatory and mechanical cellular stress in vitro. mtDNA was increased in equine synovial fluid following experimental and naturally occurring injury to the joint surface. In naturally occurring posttraumatic osteoarthritis, we found a strong positive correlation between the degree of cartilage damage and mtDNA concentration (r = 0.80, P = 0.0001). Finally, impact-induced mtDNA release was mitigated by mitoprotective treatment.
Changes in synovial fluid mtDNA occur following joint injury and correlate with the severity of cartilage damage. Mitoprotection mitigates increases in synovial fluid mtDNA suggesting that mtDNA release may reflect mitochondrial dysfunction. Further investigation of mtDNA as a potentially sensitive marker of early articular injury and response to mitoprotective therapy is warranted.
评估损伤软骨细胞中线粒体 DNA（mtDNA）的释放，并研究滑液 mtDNA 浓度在创伤后骨关节炎早期检测中的应用。
我们使用四种骨关节炎模型来测量 mtDNA 释放：体外白细胞介素-1β刺激培养的马软骨细胞、牛软骨外植体的体外机械冲击、体内马关节软骨的机械冲击和自然发生的马关节内骨折。在我们的体内模型中，一组在软骨损伤后接受关节内注射 mitoprotective 肽 SS-31。使用 qPCR 定量 mtDNA 含量。对于自然发生的关节损伤病例，临床数据（X 光片、关节镜视频）根据与退行性关节疾病相关的标准进行评分。
软骨细胞在体外炎症和机械细胞应激后的急性时间内释放 mtDNA。在关节表面受到实验性和自然损伤后，马的滑液中 mtDNA 增加。在自然发生的创伤后骨关节炎中，我们发现软骨损伤程度与 mtDNA 浓度之间存在很强的正相关（r=0.80，P=0.0001）。最后，mitoprotective 治疗减轻了冲击引起的 mtDNA 释放。
关节损伤后滑液 mtDNA 发生变化，并与软骨损伤的严重程度相关。mitoprotection 减轻了滑液 mtDNA 的增加，表明 mtDNA 释放可能反映了线粒体功能障碍。进一步研究 mtDNA 作为关节损伤早期和 mitoprotective 治疗反应的潜在敏感标志物是必要的。
