Polyphyllin I Mitigated IL-1β-Induced Chondrocytes Damage through Downregulating TWIST1 Expression.

IF 2.2 4区 医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL Current molecular medicine Pub Date : 2024-05-09 DOI:10.2174/0115665240258324231009115920
Feng Liu, Bowen Han, Deshun Yang, Xiaopeng Ji, Liangliang Yan, Chaoyong Han
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Abstract

Background: Osteoarthritis (OA) is a chronic joint disease characterized by the degradation of articular cartilage. Polyphyllin I (PPI) has anti-inflammatory effects in many diseases. However, the mechanism of PPI in OA remains unclear.

Methods: HC-a cells treated with IL-1β were identified by immunofluorescence staining and microscopic observation. The expression of collagen II and DAPI in HC-a cells was detected by immunofluorescence. The effects of gradient concentration of PPI on IL-1β-induced cell viability, apoptosis, senescence, and inflammatory factor release were detected by MTT, flow cytometry, SA-β-Gal assay and ELISA, respectively. Expressions of apoptosis-related genes, extracellular matrix (ECM)- related genes, and TWIST1 were determined by qRT-PCR and western blot as needed. The above-mentioned experiments were conducted again after TWIST1 overexpression in IL-1β-induced chondrocytes.

Results: IL-1β reduced the number of chondrocytes and the density of collagen II. PPI (0.25, 0.5, 1 µmol/L) had no effect on cell viability, but it dose-dependently elevated the inhibition of cell viability regulated by IL-1β. The elevation of cell apoptosis, senescence and expression of IL-6 and TNF-α were suppressed by PPI in a dosedependent manner. Additionally, PPI reduced the expression of cleaved caspase-3, bax, MMP-3, and MMP-13 and promoted the expression of collagen II. TWIST1 expression was diminished by PPI. TWIST1 overexpression reversed the abovementioned effects of PPI on chondrocytes.

Conclusion: PPI suppressed apoptosis, senescence, inflammation, and ECM degradation of OA chondrocytes by downregulating the expression of TWIST1.

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多叶素 I 通过下调 TWIST1 的表达减轻 IL-1β 诱导的软骨细胞损伤
背景:骨关节炎(OA)是一种以关节软骨退化为特征的慢性关节疾病。多粘菌素 I(PPI)在许多疾病中都有抗炎作用。然而,PPI 在 OA 中的作用机制仍不清楚。 方法:通过免疫荧光染色和显微镜观察鉴定经 IL-1β 处理的 HC-a 细胞。免疫荧光检测胶原蛋白II和DAPI在HC-a细胞中的表达。分别用 MTT、流式细胞仪、SA-β-Gal 检测法和 ELISA 检测了 PPI 梯度浓度对 IL-1β 诱导的细胞活力、凋亡、衰老和炎症因子释放的影响。凋亡相关基因、细胞外基质(ECM)相关基因和 TWIST1 的表达根据需要通过 qRT-PCR 和 western 印迹进行检测。在 IL-1β 诱导的软骨细胞中过表达 TWIST1 后,再次进行上述实验。 结果IL-1β减少了软骨细胞的数量和胶原蛋白II的密度。PPI(0.25、0.5、1 µmol/L)对细胞存活率没有影响,但其剂量依赖性提高了 IL-1β 对细胞存活率的抑制作用。PPI 以剂量依赖的方式抑制了细胞凋亡、衰老以及 IL-6 和 TNF-α 表达的增加。此外,PPI 还降低了裂解的 caspase-3、bax、MMP-3 和 MMP-13 的表达,并促进了胶原蛋白 II 的表达。PPI降低了TWIST1的表达。过表达 TWIST1 可逆转 PPI 对软骨细胞的上述影响。 结论PPI 通过下调 TWIST1 的表达抑制了 OA 软骨细胞的凋亡、衰老、炎症和 ECM 降解。
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来源期刊
Current molecular medicine
Current molecular medicine 医学-医学:研究与实验
CiteScore
5.00
自引率
4.00%
发文量
141
审稿时长
4-8 weeks
期刊介绍: Current Molecular Medicine is an interdisciplinary journal focused on providing the readership with current and comprehensive reviews/ mini-reviews, original research articles, short communications/letters and drug clinical trial studies on fundamental molecular mechanisms of disease pathogenesis, the development of molecular-diagnosis and/or novel approaches to rational treatment. The reviews should be of significant interest to basic researchers and clinical investigators in molecular medicine. Periodically the journal invites guest editors to devote an issue on a basic research area that shows promise to advance our understanding of the molecular mechanism(s) of a disease or has potential for clinical applications.
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