Knee osteoarthritis (KOA) is a chronic joint disease characterized by the degeneration of articular cartilage. In this study, we explored the potential therapeutic effects of platelet-rich plasma (PRP) and identified molecular targets for treating KOA. A rat model of KOA was established via the Hulth method and primary knee joint chondrocytes were isolated to evaluate the effects of PRP and shRNA targeting p65 (sh-p65). ELISA was used to detect inflammatory factors, including IL-6, IL-1β, and TNF-α. HE staining, Safranin O/Fast Green staining and Masson staining were performed to evaluate the morphology of articular cartilage, followed by detection of p65, COL2A1, ACAN, MMP13, and ADAMTS5 expression. The proliferation and apoptosis of primary knee chondrocytes were detected by the CCK-8 assay and TUNEL staining, respectively. Treatment with either PRP or sh-p65 decreased IL-6, IL-1β, and TNF-α levels in the peripheral blood of KOA rats and chondrocyte culture supernatants, increased COL2A1 and ACAN levels, and decreased MMP13 and ADAMTS5 expression. Furthermore, administration of PRP or sh-p65 exerted protective effects on articular cartilage, enhanced the vitality of knee joint chondrocytes, and inhibited apoptosis. Collectively, PRP inhibited inflammation, promoted chondrocyte proliferation and cartilage matrix secretion, and induced cartilage regeneration by suppressing p65 expression; these effects allow PRP to alleviate KOA progression. P65-based targeted therapy administered in combination with PRP might be a promising strategy for treating KOA.

膝骨关节炎（KOA）是一种以关节软骨退化为特征的慢性关节疾病。在这项研究中，我们探索了富血小板血浆 (PRP) 的潜在治疗作用，并确定了治疗 KOA 的分子靶点。采用Hulth法建立KOA大鼠模型，分离原代膝关节软骨细胞，评价PRP和靶向p65的shRNA（sh-p65）的作用。采用ELISA法检测炎症因子，包括IL-6、IL-1β、TNF-α。采用HE染色、Safranin O/Fast Green染色和Masson染色评价关节软骨形态，检测p65、COL2A1、ACAN、MMP13和ADAMTS5表达。分别采用CCK-8法和TUNEL染色检测原代膝关节软骨细胞的增殖和凋亡。用 PRP 或 sh-p65 治疗可降低 KOA 大鼠外周血和软骨细胞培养物上清液中 IL-6、IL-1β 和 TNF-α 的水平，增加 COL2A1 和 ACAN 的水平，并降低 MMP13 和 ADAMTS5 的表达。此外，给予PRP或sh-p65对关节软骨有保护作用，增强膝关节软骨细胞的活力，抑制细胞凋亡。总的来说，PRP 可以抑制炎症，促进软骨细胞增殖和软骨基质分泌，并通过抑制 p65 表达来诱导软骨再生。这些作用使得 PRP 能够缓解 KOA 的进展。基于 P65 的靶向治疗与 PRP 联合使用可能是治疗 KOA 的一种有前途的策略。