Department of Orthopedics, Liaocheng Third People's Hospital, Liaocheng, China.
Int J Immunopathol Pharmacol. 2019 Jan-Dec;33:2058738418824521. doi: 10.1177/2058738418824521.
Tripterine, also known as celastrol, is a main natural ingredient in Tripterygium wilfordii. Tripterine has a variety of pharmacological functions, and the therapeutic potential of tripterine in many kinds of inflammation-linked diseases has been revealed. However, the function of tripterine on osteoarthritis still remains unclear. The objective of this study was to study the function of tripterine (TPR) on lipopolysaccharide (LPS)-injured chondrocyte. ATDC5 cells were treated with tripterine after LPS stimulation and then cell survival, the release of pro-inflammatory cytokines, and the expression of chondrogenic differentiation-associated proteins were assessed by performing CCK-8, flow cytometry, reverse transcription quantitative polymerase chain reaction (RT-qPCR), enzyme-linked immunosorbent assay (ELISA), and Western blot. Moreover, the expression of miR-223 and core factors in PI3K/AKT and nuclear factor kappa B (NF-κB) signaling was tested by RT-qPCR/Western blot. LPS stimulation significantly reduced ATDC5 cells viability, induced apoptosis, and increased the release of interleukin (IL)-6 and tumor necrosis factor (TNF)-α. Tripterine protected ATDC5 cells against LPS-induced chondrocyte loss and the release of IL-6 and TNF-α. miR-223 was down-regulated by LPS, while was up-regulated by tripterine. The protective actions of tripterine were eliminated when miR-223 was silenced. Besides, tripterine inhibited hypertrophic differentiation induced by LPS, and the inhibitory effects of tripterine on hypertrophic differentiation could be abolished when miR-223 was silenced. Furthermore, tripterine activated PI3K/AKT pathway and deactivated NF-κB pathway. And the regulatory effects of tripterine on these two pathways were abolished by miR-223 silence. This study revealed that tripterine protected ATDC5 cells against LPS-induced cell damage possibly via up-regulation of miR-223 and modulation of NF-κB and PI3K/AKT pathways.
雷公藤红素，又称 celastrol，是雷公藤的主要天然成分。雷公藤红素具有多种药理作用，其在多种炎症相关疾病中的治疗潜力已被揭示。然而，雷公藤红素在骨关节炎中的作用尚不清楚。本研究旨在研究雷公藤红素（TPR）对脂多糖（LPS）损伤软骨细胞的作用。用 LPS 刺激 ATDC5 细胞后用 TPR 处理，然后通过 CCK-8、流式细胞术、逆转录定量聚合酶链反应（RT-qPCR）、酶联免疫吸附测定（ELISA）和 Western blot 评估细胞存活率、促炎细胞因子释放和软骨分化相关蛋白的表达。此外，通过 RT-qPCR/Western blot 检测 miR-223 和 PI3K/AKT 和核因子 kappa B（NF-κB）信号通路中的核心因子的表达。LPS 刺激显著降低 ATDC5 细胞活力，诱导细胞凋亡，并增加白细胞介素（IL）-6 和肿瘤坏死因子（TNF）-α的释放。雷公藤红素可保护 ATDC5 细胞免受 LPS 诱导的软骨细胞丢失和 IL-6 和 TNF-α的释放。miR-223 被 LPS 下调，而被 TPR 上调。沉默 miR-223 可消除 TPR 的保护作用。此外，雷公藤红素抑制 LPS 诱导的肥大分化，沉默 miR-223 可消除雷公藤红素对肥大分化的抑制作用。此外，雷公藤红素激活 PI3K/AKT 通路并失活 NF-κB 通路。沉默 miR-223 可消除雷公藤红素对这两条通路的调节作用。本研究表明，雷公藤红素通过上调 miR-223 并调节 NF-κB 和 PI3K/AKT 通路来保护 ATDC5 细胞免受 LPS 诱导的细胞损伤。
