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Abstract：
Osteoarthritis (OA) is the most prevalent degenerative joint disease worldwide. Effective management for early-stage OA is crucial. Denosumab (DS) has been widely used to treat osteoporosis (OP) and rheumatoid arthritis, but its potential for managing OA remains clear. We assessed the effects of DS on osteoclast activity and chondrocyte apoptosis using tartrate-resistant acid phosphatase (TRAP) assay, quantitative real-time polymerase chain reaction (qRT-PCR), flow cytometry, and TUNEL staining. To assess the impact of DS on the NF-κB pathway, we performed Western blot and immunofluorescence staining. Additionally, we used an OA model to explore the influence of DS on subchondral bone remodeling and cartilage degeneration in vivo. We found that DS hindered receptor activator of nuclear factor kappa B ligand (RANKL)-induced osteoclastogenesis by inhibiting the activity of the NF-κB pathway. Besides, DS alleviated reactive oxygen species (ROS)-induced apoptosis in chondrocytes by regulating the expression of genes related to apoptosis. Moreover, we observed an attenuation of OA-related subchondral bone remodeling and cartilage degeneration in vivo. Our findings indicate that DS could effectively suppress osteoclast activity and chondrocyte apoptosis, thereby mitigating OA-related subchondral bone remodeling and cartilage degeneration. These results provide a mechanistic basis for using DS to treat OA.
摘要：
骨关节炎(OA)是世界范围内最常见的退行性关节疾病。有效管理早期OA至关重要。Denosumab（DS）已被广泛用于治疗骨质疏松症（OP）和类风湿性关节炎，但其管理OA的潜力仍然很明显。我们使用抗酒石酸酸性磷酸酶（TRAP）测定法评估DS对破骨细胞活性和软骨细胞凋亡的影响。定量实时聚合酶链反应（qRT-PCR），流式细胞术,和TUNEL染色。为了评估DS对NF-κB通路的影响，我们进行了蛋白质印迹和免疫荧光染色。此外,我们使用OA模型来探讨DS对体内软骨下骨重塑和软骨退变的影响。我们发现，核因子κB配体（RANKL）的DS受阻受体激活剂通过抑制NF-κB途径的活性来诱导破骨细胞生成。此外,DS通过调节凋亡相关基因的表达减轻活性氧（ROS）诱导的软骨细胞凋亡。此外，我们观察到体内OA相关的软骨下骨重塑和软骨退变的减弱。我们的发现表明，DS可以有效抑制破骨细胞活性和软骨细胞凋亡，从而减轻OA相关的软骨下骨重塑和软骨退变。这些结果为使用DS治疗OA提供了机制基础。
