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首页> 外文期刊>Journal of orthopaedic research >Knee fibrosis is associated with the development of osteoarthritis in a murine model of tibial compression
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Knee fibrosis is associated with the development of osteoarthritis in a murine model of tibial compression

机译：膝盖纤维化与胫骨压缩小鼠模型中的骨关节炎的发育有关

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Fibrosis in the synovium and infrapatellar fat pad (IFP) is frequently observed in knee osteoarthritis (OA) and is often correlated with joint pain and stiffness. However, the mechanisms underpinning the development of knee fibrosis in OA are relatively poorly understood. In this study, we used a combination of histological, immunohistochemical, and multiplex gene expression analyses to characterize the fibrosis that develops in a mouse model of load-induced OA. Histological evaluation showed the time-dependent development of fibrosis in the synovium, capsule, and IFP of loaded limbs of male 11-week-old mice. The development of load-induced fibrosis was accompanied primarily by proliferation, expansion, and activation of the stromal compartment, and by increased macrophage presence evidenced by increased F4/80 and MAC2 positive immunostaining. The presence of B and T-cells was minimal in both control and loaded limbs, but CD3-positive immunostaining was significantly higher in C57BL/6J at 2 weeks after loading, indicating an increased presence of T-cells. Using NanoString gene expression analyses of human and mouse tissues, we found that mice subjected to cyclic loading recapitulated the gene expression profile observed in human fibrotic tissues, including increased expression of collagen genes. Together, our results indicate that this well-controlled nonsurgical mouse model can be used to study the mechanisms underpinning the development of knee fibrosis, and potentially to test targeted strategies to prevent the development of fibrosis and stiffness of the knee.
机译：滑膜和髌下脂肪垫（IFP）中的纤维化在膝骨关节炎（OA）中经常被观察到，并且通常与关节疼痛和僵硬相关。然而，骨性关节炎膝关节纤维化发生的机制相对缺乏了解。在这项研究中，我们结合组织学、免疫组织化学和多重基因表达分析来描述在负荷诱导的OA小鼠模型中形成的纤维化。组织学评估显示，11周龄雄性小鼠负重肢体的滑膜、关节囊和IFP中纤维化的发展具有时间依赖性。负荷诱导的纤维化的发展主要伴随基质室的增殖、扩张和激活，以及巨噬细胞的存在增加，表现为F4/80和MAC2阳性免疫染色增加。在对照组和负重肢体中，B细胞和T细胞的存在都很小，但在负重后2周，C57BL/6J中的CD3阳性免疫染色显著增加，表明T细胞的存在增加。通过对人类和小鼠组织进行纳米串基因表达分析，我们发现，经受循环负荷的小鼠重现了在人类纤维化组织中观察到的基因表达谱，包括胶原基因的表达增加。总之，我们的研究结果表明，这种控制良好的非手术小鼠模型可用于研究支持膝关节纤维化发展的机制，并可能用于测试有针对性的策略，以防止膝关节纤维化和僵硬的发展。

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