Siengdee P, Pradit W, Euppayo T, Chomdej S, Nganvongpanit K
Animal Bone and Joint Research Laboratory, Department of Veterinary Biosciences and Public Health, Faculty of Veterinary Medicine, Chiang Mai University, Chiang Mai, Thailand.
Department of Biology, Faculty of Science, Chiang Mai University, Chiang Mai, Thailand.
J Vet Pharmacol Ther. 2017 Dec;40(6):604-617. doi: 10.1111/jvp.12401. Epub 2017 Mar 19.
Cephalosporins (CEFs) are antibiotics frequently used to treat bone infections and septic arthritis. The effects of CEFs on chondrocytes have not been studied until now. Cefazolin (cef1) and ceftriaxone (cef3), first-and third-generation CEFs, were selected to investigate their direct effects on normal and osteoarthritic (OA) primary canine chondrocytes, which were either nonstimulated or stimulated with the pro-inflammatory cytokine IL-1β. In our results, treatment with CEFs increased the negative effects on both conditioned normal and OA chondrocytes, especially when applied to IL-1β-stimulated cells (inflammatory stimulus). CEFs significantly decreased cell viability and induced apoptotic cell death in both normal and OA chondrocytes; moreover, treatment with cef1 caused necrotic cell death in OA chondrocytes. Cef3 treatment could increase s-GAG synthesis in normal cells preincubated with IL-1β, while cef1 had no significant effect. The expression of TNF was clearly downregulated after cef3 treatments, whereas it was upregulated after cef1 treatments. However, cef3 induced stronger downregulation of TIMP1 and the extracellular matrix component genes COL2A1 and ACAN. In conclusion, these results suggest both the cytotoxic effects of CEFs and their adverse effects on chondrogenic marker genes at the transcriptional level, which provide additional insight into the clinical application of cef1 and cef3.
头孢菌素（CEFs）是常用于治疗骨感染和化脓性关节炎的抗生素。迄今为止，尚未对头孢菌素对软骨细胞的影响进行研究。选择第一代和第三代头孢菌素头孢唑林（cef1）和头孢曲松（cef3），以研究它们对正常和骨关节炎（OA）原代犬软骨细胞的直接影响，这些细胞未受刺激或用促炎细胞因子IL-1β刺激。在我们的结果中，头孢菌素处理增加了对正常和OA条件性软骨细胞的负面影响，特别是当应用于IL-1β刺激的细胞（炎症刺激）时。头孢菌素显著降低了正常和OA软骨细胞的细胞活力并诱导了凋亡性细胞死亡；此外，cef1处理导致OA软骨细胞坏死性细胞死亡。头孢曲松处理可增加与IL-1β预孵育的正常细胞中的硫酸糖胺聚糖（s-GAG）合成，而cef1则无显著影响。头孢曲松处理后TNF的表达明显下调，而cef1处理后TNF表达上调。然而，头孢曲松诱导TIMP1以及细胞外基质成分基因COL2A1和ACAN的下调更强。总之，这些结果表明头孢菌素的细胞毒性作用及其在转录水平对软骨生成标记基因的不利影响，这为cef1和cef3的临床应用提供了更多见解。
