Pang Kok-Lun, Chow Yoke Yue, Leong Lek Mun, Law Jia Xian, Ghafar Norzana Abd, Soelaiman Ima Nirwana, Chin Kok-Yong
Department of Pharmacology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur 56000, Malaysia.
Department of Orthopaedic and Trauma Medicine, Deanery of Clinical Sciences, The University of Edinburgh, Edinburgh EH16 4SB, UK.
Life (Basel). 2021 Mar 25;11(4):272. doi: 10.3390/life11040272.
Osteoarthritis (OA) is the most common degenerative joint disease characterised by chondrocyte cell death. An in vitro model of chondrocyte cell death may facilitate drug discovery in OA management. In this study, the cytotoxicity and mode of cell death of SW1353 chondrocytes treated with 24 h of OA inducers, including interleukin-1β (IL-1β), hydrogen peroxide (HO) and monosodium iodoacetate (MIA), were investigated. The microscopic features, oxidative (isoprostane) and inflammatory markers (tumour necrosis factor-alpha; TNF-α) for control and treated cells were compared. Our results showed that 24 h of HO and MIA caused oxidative stress and a concentration-dependent reduction of SW1353 cell viability without TNF-α level upregulation. HO primarily induced chondrocyte apoptosis with the detection of blebbing formation, cell shrinkage and cellular debris. MIA induced S-phase arrest on chondrocytes with a reduced number of attached cells but without significant cell death. On the other hand, 24 h of IL-1β did not affect the cell morphology and viability of SW1353 cells, with a significant increase in intracellular TNF-α levels without inducing oxidative stress. In conclusion, each OA inducer exerts differential effects on SW1353 chondrocyte cell fate. IL-1β is suitable in the inflammatory study but not for chondrocyte cell death. HO and MIA are suitable for inducing chondrocyte cell death and growth arrest, respectively.
骨关节炎（OA）是最常见的以软骨细胞死亡为特征的退行性关节疾病。软骨细胞死亡的体外模型可能有助于骨关节炎治疗药物的研发。在本研究中，我们调查了用骨关节炎诱导剂（包括白细胞介素-1β（IL-1β）、过氧化氢（HO）和碘乙酸钠（MIA））处理24小时的SW1353软骨细胞的细胞毒性和细胞死亡模式。比较了对照细胞和处理细胞的微观特征、氧化（异前列腺素）和炎症标志物（肿瘤坏死因子-α；TNF-α）。我们的结果表明，24小时的HO和MIA会引起氧化应激，并导致SW1353细胞活力呈浓度依赖性降低，而TNF-α水平没有上调。HO主要诱导软骨细胞凋亡，表现为出现气泡形成、细胞收缩和细胞碎片。MIA诱导软骨细胞S期阻滞，贴壁细胞数量减少，但无明显细胞死亡。另一方面，24小时的IL-1β不影响SW1353细胞的形态和活力，细胞内TNF-α水平显著升高，但不诱导氧化应激。总之，每种骨关节炎诱导剂对SW1353软骨细胞命运都有不同的影响。IL-1β适用于炎症研究，但不适用于软骨细胞死亡研究。HO和MIA分别适用于诱导软骨细胞死亡和生长停滞。
