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

Synovial fluid mitochondrial DNA concentration reflects the degree of cartilage damage after naturally occurring articular injury.
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滑液线粒体DNA浓度反映了自然发生的关节损伤后软骨损伤的程度。

DOI:
10.1016/j.joca.2023.03.013
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发表时间:
2023
影响因子:
7
通讯作者:
Delco,ML
Delco,ML
中科院分区:
医学2区
文献类型:
--
作者:
Seewald,LA;Sabino,IG;Montney,KL;Delco,ML

文献摘要

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目的评价损伤软骨细胞线粒体DNA(mtDNA)的释放,并探讨关节滑液mtDNA浓度在创伤后骨关节炎早期检测中的作用。方法我们采用四种骨关节炎模型测定mtDNA的释放:体外培养的马软骨细胞的白细胞介素1β刺激,牛软骨外植体的体外力学影响,马关节软骨的体内力学影响,以及自然发生的马关节内骨折。在我们的活体模型中,一组在软骨损伤后关节内注射线粒体保护肽SS-31。使用qPCR定量mtDNA含量。对于自然发生的情况下,关节损伤,临床数据(X光片,关节镜下的视频片段)进行了评分标准与退行性关节diseases.ResultsChondrocytes释放线粒体DNA在急性时间框架后,炎症和机械细胞stressin体外。实验性和自然发生的关节表面损伤后,马滑液中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浓度之间存在强正相关(r= 0.80,P = 0.0001)。最后,mitoprotective treatment.ConclusionChanges在滑液中的线粒体DNA发生后,关节损伤,并与软骨损伤的严重程度相关的影响诱导的线粒体DNA释放减轻。线粒体保护减轻滑液mtDNA的增加,表明mtDNA释放可能反映线粒体功能障碍。进一步研究线粒体DNA作为早期关节损伤和对线粒体保护治疗反应的潜在敏感标志物是必要的。
ObjectiveTo evaluate mitochondrial DNA (mtDNA) release from injured chondrocytes and investigate the utility of synovial fluid mtDNA concentration in early detection of posttraumatic osteoarthritis.MethodWe measured mtDNA release using four models of osteoarthritis:in vitrointerleukin-1β stimulation of cultured equine chondrocytes,ex vivomechanical impact of bovine cartilage explants,in vivomechanical impact of equine articular cartilage, and naturally occurring equine intraarticular fracture. In ourin vivomodel, 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.ResultsChondrocytes released mtDNA in the acute time frame following inflammatory and mechanical cellular stressin 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.ConclusionChanges 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.