Department of Pharmacy, The Second Affiliated Hospital of Qiqihar Medical University, Qiqihar, Heilongjiang 161006, China.
Department of Orthopaedics, The First Affiliated Hospital of Qiqihar Medical University, Qiqihar, Heilongjiang 161000, China.
Int Immunopharmacol. 2024 Dec 25;143(Pt 2):113417. doi: 10.1016/j.intimp.2024.113417. Epub 2024 Oct 23.
Interleukin-1β (IL-1β) plays a crucial role in cartilage degeneration by inducing inflammatory cascades in chondrocytes, impairing their normal biological functions. Long non-coding RNA NKILA (lncRNA NKILA) has been implicated in osteoarthritis (OA), but its specific molecular mechanisms remain unclear. This study aims to elucidate the function and molecular regulatory mechanism of lncRNA NKILA in articular chondrocytes under IL-1β stimulation.
Primary human articular chondrocytes were cultured to investigate the effects of IL-1β on chondrocyte proliferation, apoptosis, and extracellular matrix metabolism. We employed Reverse Transcription Quantitative Polymerase Chain Reaction (RT-qPCR), western blot, flow cytometry, immunofluorescence, and nuclear mass separation assays to explore the interaction between lncRNA NKILA and the NFκB signaling pathway. Additionally, animal experiments were conducted to evaluate the therapeutic potential of modulating lncRNA NKILA expression in vivo.
IL-1β treatment led to decreased chondrocyte proliferation and increased apoptosis. Our study demonstrated that IL-1β downregulates lncRNA NKILA, which weakens its inhibitory effect on the NFκB (Nuclear Factor Kappa B) signaling pathway. This downregulation results in increased NFκB activity and exacerbates chondrocyte degeneration. Notably, the upregulation of lncRNA NKILA significantly alleviated OA symptoms, indicating that NKILA could be a promising therapeutic target.
IL-1β reduces lncRNA NKILA expression, weakening its inhibition of NFκB signaling and promoting articular chondrocyte degeneration. Enhancing lncRNA NKILA expression offers a promising approach to mitigating OA, suggesting that NKILA could serve as a potential therapeutic target for OA treatment.
白细胞介素-1β（IL-1β）通过诱导软骨细胞中的炎症级联反应，损害其正常的生物学功能，在软骨退变中发挥关键作用。长链非编码 RNA NKILA（lncRNA NKILA）已被牵连到骨关节炎（OA）中，但它的具体分子机制尚不清楚。本研究旨在阐明 lncRNA NKILA 在 IL-1β刺激下关节软骨细胞中的功能和分子调控机制。
培养原代人关节软骨细胞，研究 IL-1β对软骨细胞增殖、凋亡和细胞外基质代谢的影响。我们采用逆转录定量聚合酶链反应（RT-qPCR）、western blot、流式细胞术、免疫荧光和核质分离实验来探索 lncRNA NKILA 与 NFκB 信号通路的相互作用。此外，还进行了动物实验来评估体内调节 lncRNA NKILA 表达的治疗潜力。
IL-1β 处理导致软骨细胞增殖减少和凋亡增加。我们的研究表明，IL-1β 下调 lncRNA NKILA，从而削弱其对 NFκB（核因子 kappa B）信号通路的抑制作用。这种下调导致 NFκB 活性增加，加剧软骨细胞退变。值得注意的是，上调 lncRNA NKILA 可显著缓解 OA 症状，表明 NKILA 可能是一个有前途的治疗靶点。
IL-1β 降低 lncRNA NKILA 的表达，削弱其对 NFκB 信号的抑制作用，促进关节软骨细胞退变。增强 lncRNA NKILA 的表达为减轻 OA 提供了一种有前途的方法，表明 NKILA 可能成为 OA 治疗的潜在治疗靶点。
