BackgroundTraumatic cartilage injury is an important cause of osteoarthritis (OA) and limb disability, and toll‐like receptors (TLRs) mediated innate immune response has been confirmed to play a crucial role in cartilage injury. In the previous study, we found that the activation of TLR8 molecules in injured articular cartilage was more obvious than other TLRs by establishing an animal model of knee impact injury in rabbits, and the changes of TLR8 molecules could significantly affect the process of articular cartilage injury and repair.ObjectiveTo verify how mir‐99a‐5p regulates TLR8 receptor mediated innate immune response to treat traumatic cartilage injury.MethodsThe impact of a heavy object on the medial condyle of the rabbit's knee joint caused damage to the medial condylar cartilage. Through pathological and imaging analysis, it was demonstrated whether the establishment of an animal model of traumatic cartilage injury was successful. Establishing a cell model by virus transfection of chondrocytes to demonstrate the role of TLR8 in the innate immune response to impact cartilage injury. Through transcriptome sequencing, potential targets of TLR8, mir‐99a‐5p, were predicted, and basic experiments were conducted to demonstrate how they interact with innate immune responses to impact cartilage damage.ResultsTLR8 is a receptor protein of the immune system, which is widely expressed in immune cells. In our study, we found that TLR8 expression is localized in lysosomes and endosomes. Mir‐99a‐5p can negatively regulate TLR8 to activate PI3K‐AKT molecular pathway and aggravate cartilage damage. Inhibiting TLR8 expression can effectively reduce the incidence of articular cartilage damage.ConclusionBased on the results from this study, mir‐99a‐5p may be an effective molecular marker for predicting traumatic cartilage injury and targeting TLR8 is a novel and promising approach for the prevention or early treatment of cartilage damage.

中文翻译：

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mir-99a-5p负调节TLR8受体介导的先天免疫反应在兔膝关节软骨损伤中的实验研究

背景创伤性软骨损伤是骨关节炎（OA）和肢体残疾的重要原因，Toll样受体（TLRs）介导的先天免疫反应已被证实在软骨损伤中发挥着至关重要的作用。在前期研究中，我们通过建立家兔膝关节冲击损伤动物模型，发现损伤关节软骨中TLR8分子的激活较其他TLR更为明显，且TLR8分子的变化能够显着影响关节软骨损伤的进程。目的验证mir-99a-5p如何调节TLR8受体介导的先天免疫反应治疗创伤性软骨损伤。方法重物撞击家兔膝关节内侧髁造成内侧髁软骨损伤。通过病理和影像学分析，证明创伤性软骨损伤动物模型的建立是否成功。通过病毒转染软骨细胞建立细胞模型，以证明 TLR8 在影响软骨损伤的先天免疫反应中的作用。通过转录组测序，预测了TLR8的潜在靶标mir-99a-5p，并进行了基础实验来证明它们如何与先天免疫反应相互作用以影响软骨损伤。结果TLR8是免疫系统的受体蛋白，广泛应用于在免疫细胞中表达。在我们的研究中，我们发现 TLR8 表达位于溶酶体和内体中。 Mir-99a-5p可负向调节TLR8激活PI3K-AKT分子通路，加重软骨损伤。抑制TLR8表达可以有效降低关节软骨损伤的发生率。结论根据本研究结果，mir-99a-5p可能是预测创伤性软骨损伤的有效分子标志物，靶向TLR8是预防或预防关节软骨损伤的一种新颖且有前景的方法。及早治疗软骨损伤。