Center of Experimental Orthopaedics, Saarland University, 66421 Homburg, Germany.
Department of Orthopaedic Surgery, Saarland University Medical Center, 66421 Homburg, Germany.
Sci Transl Med. 2019 Sep 4;11(508). doi: 10.1126/scitranslmed.aax6775.
Articular cartilage damage occurring during early osteoarthritis (OA) is a key event marking the development of the disease. Here, we modeled early human OA by gathering detailed spatiotemporal data from surgically induced knee OA development in sheep. We identified a specific topographical pattern of osteochondral changes instructed by a defined meniscal injury, showing that both cartilage and subchondral bone degeneration are initiated from the region adjacent to the damage. Alterations of the subarticular spongiosa arising locally and progressing globally disturbed the correlations of cartilage with subchondral bone seen at homeostasis and were indicative of disease progression. We validated our quantitative findings against human OA, showing a similar pattern of early OA correlating with regions of meniscal loss and an analogous late critical disturbance within the entire osteochondral unit. This translational model system can be used to elucidate mechanisms of OA development and provides a roadmap for investigating regenerative therapies.
在早期骨关节炎 (OA) 过程中发生的关节软骨损伤是标志疾病发展的关键事件。在这里，我们通过收集绵羊手术诱导的膝 OA 发展过程中的详细时空数据，建立了早期人类 OA 模型。我们确定了一种特定的软骨下骨变化的地形模式，由明确的半月板损伤指导，表明软骨和软骨下骨退化均从损伤附近区域开始。局部出现的亚关节松质骨改变并逐渐影响全局，破坏了在体内平衡时观察到的软骨与软骨下骨之间的相关性，提示疾病进展。我们将我们的定量发现与人类 OA 进行了验证，显示出与半月板缺失相关的早期 OA 的相似模式，以及整个软骨下骨单元内类似的晚期临界干扰。这种转化模型系统可用于阐明 OA 发展的机制，并为研究再生疗法提供了路线图。
