Department of Orthopaedic Surgery, Duke University Medical Center, Box 3389, Durham, North Carolina 27710, USA.
J Orthop Res. 2013 Aug;31(8):1283-92. doi: 10.1002/jor.22348. Epub 2013 Apr 25.
Post-traumatic arthritis (PTA) frequently develops after intra-articular fracture of weight bearing joints. Loss of cartilage viability and post-injury inflammation have both been implicated as possible contributing factors to PTA progression. To further investigate chondrocyte response to impact and fracture, we developed a blunt impact model applying 70%, 80%, or 90% surface-to-surface compressive strain with or without induction of an articular fracture in a cartilage explant model. Following mechanical loading, chondrocyte viability, and apoptosis were assessed. Culture media were evaluated for the release of double-stranded DNA (dsDNA) and immunostimulatory activity via nuclear factor kappa B (NF-κB) activity in Toll-like receptor (TLR) -expressing Ramos-Blue reporter cells. High compressive strains, with or without articular fracture, resulted in significantly reduced chondrocyte viability. Blunt impact at 70% strain induced a loss in viability over time through a combination of apoptosis and necrosis, whereas blunt impact above 80% strain caused predominantly necrosis. In the fracture model, a high level of primarily necrotic chondrocyte death occurred along the fracture edges. At sites away from the fracture, viability was not significantly different than controls. Interestingly, both dsDNA release and NF-κB activity in Ramos-Blue cells increased with blunt impact, but was only significantly increased in the media from fractured cores. This study indicates that the mechanism of trauma determines the type of chondrocyte death and the potential for post-injury inflammation.
创伤后关节炎（PTA）常在负重关节关节内骨折后发生。软骨细胞活力丧失和损伤后炎症都可能是 PTA 进展的促成因素。为了进一步研究软骨细胞对冲击和骨折的反应，我们在软骨外植体模型中开发了一种钝性冲击模型，应用 70%、80%或 90%的表面到表面压缩应变，同时或不诱导关节骨折。在机械加载后，评估软骨细胞活力和细胞凋亡。通过核因子 kappa B（NF-κB）在表达 Toll 样受体（TLR）的 Ramos-Blue 报告细胞中的活性，评估培养基中双链 DNA（dsDNA）的释放和免疫刺激性活性。有或没有关节骨折的高压缩应变导致软骨细胞活力显著降低。70%应变的钝性冲击随着时间的推移通过凋亡和坏死的组合导致活力丧失，而 80%以上应变的钝性冲击主要导致坏死。在骨折模型中，骨折边缘处主要发生大量坏死性软骨细胞死亡。在远离骨折的部位，活力与对照相比没有显著差异。有趣的是，Ramos-Blue 细胞中的 dsDNA 释放和 NF-κB 活性随着钝性冲击而增加，但仅在骨折核心的培养基中显著增加。这项研究表明，创伤的机制决定了软骨细胞死亡的类型和损伤后炎症的潜力。
