Institute of Biomedical & Environmental Health Research, University of the West of Scotland, Paisley, PA1 2BE, UK.
Institute of Ageing and Chronic Disease, University of Liverpool, WH Duncan Building, West Derby Street, Liverpool, L7 8TX, UK.
Osteoarthritis Cartilage. 2019 Dec;27(12):1800-1810. doi: 10.1016/j.joca.2019.05.027. Epub 2019 Jul 5.
Joint injury involving destabilisation of the joint and damage to the articular cartilage (e.g., sports-related injury) can result in accelerated post-traumatic osteoarthritis (PTOA). Destabilised medial meniscotibial ligament (DMM) surgery is one of the most commonly used murine models and whilst it recapitulates Osteoarthritis (OA) pathology, it does not necessarily result in multi-tissue injury, as occurs in PTOA. We hypothesised that simultaneous cartilage damage and joint destabilisation would accelerate the onset of OA pathology.
OA was induced in C57BL/6 mice via (a) DMM, (b) microblade scratches of articular cartilage (CS) or (c) combined DMM and cartilage scratch (DCS). Mice were culled 7, 14 and 28 days post-surgery. Microcomputed tomography (μCT) and histology were used to monitor bone changes and inflammation. Dynamic weight bearing, an indirect measure of pain, was assessed on day 14.
Osteophytogenesis analysis via μCT revealed that osteophytes were present in all groups at days 7 and 14 post-surgery. However, in DCS, osteophytes were visually larger and more numerous when compared with DMM and cartilage scratch (CS). Histological assessment of cartilage at day 14 and 28, revealed significantly greater damage in DCS compared with DMM and CS. Furthermore, a significant increase in synovitis was observed in DCS. Finally, at day 14 osteophyte numbers correlated with changes in dynamic weight bearing.
Joint destabilisation when combined with simultaneous cartilage injury accelerates joint deterioration, as seen in PTOA. Thus, DCS provides a novel and robust model for investigating multiple pathological hallmarks, including osteophytogenesis, cartilage damage, synovitis and OA-related pain.
涉及关节不稳定和关节软骨损伤的关节损伤（例如与运动相关的损伤）可导致创伤后加速性骨关节炎（PTOA）。内侧半月板胫骨韧带不稳定（DMM）手术是最常用的鼠模型之一，尽管它再现了骨关节炎（OA）病理学，但不一定会导致 PTOA 中发生的多组织损伤。我们假设同时发生软骨损伤和关节不稳定会加速 OA 病理学的发生。
通过（a）DMM、（b）关节软骨微刃划痕（CS）或（c）DMM 和软骨划痕的组合（DCS）在 C57BL/6 小鼠中诱导 OA。手术后 7、14 和 28 天处死小鼠。使用微计算机断层扫描（μCT）和组织学监测骨变化和炎症。在第 14 天评估动态负重，这是疼痛的间接测量。
通过 μCT 进行的骨赘发生分析显示，手术后第 7 天和第 14 天所有组均存在骨赘。然而，在 DCS 中，与 DMM 和软骨划痕（CS）相比，骨赘在视觉上更大且更多。在第 14 天和第 28 天对软骨进行组织学评估时，发现 DCS 中的软骨损伤明显大于 DMM 和 CS。此外，在 DCS 中观察到滑膜炎明显增加。最后，在第 14 天，骨赘数量与动态负重的变化相关。
当与同时发生的软骨损伤相结合时，关节不稳定会加速关节恶化，如 PTOA 所见。因此，DCS 为研究包括骨赘形成、软骨损伤、滑膜炎和与 OA 相关的疼痛在内的多种病理特征提供了一种新颖而强大的模型。
