研究动态
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柳氮磺吡啶是一种有效的胱氨酸-谷氨酸转运蛋白抑制剂,可增强犬脂肪干细胞的成骨分化。

Sulfasalazine, a potent cystine-glutamate transporter inhibitor, enhances osteogenic differentiation of canine adipose-derived stem cells.

发表日期:2023 Oct 20
作者: Harumichi Itoh, Kenji Tani, Hiroshi Sunahara, Yuki Nemoto, Munekazu Nakaichi, Hiro Horikirizono, Kazuhito Itamoto
来源: Arthritis & Rheumatology

摘要:

胱氨酸-谷氨酸转运蛋白 (xCT) 是一种质膜转运蛋白,可输入胱氨酸并间接有助于与细胞内谷胱甘肽水平增加相关的氧化应激抵抗。犬脂肪干细胞 (CADDSC) 包括 xCT 阳性亚群,在体外成骨分化过程中显示出相对较低的成骨标志物表达。柳氮磺吡啶 (SSZ) 是一种用于治疗类风湿性关节炎的药物,可抑制癌细胞中 xCT 的表达。在这项研究中,我们发现 100 µM SSZ 处理显着抑制 CADSC 中 xCT mRNA 的表达,但在相同条件下没有显着影响细胞增殖。此外,这种治疗降低了细胞内谷胱甘肽浓度。在体外成骨分化过程中,50 µM 和 100 µM 的 SSZ 处理显着增加了茜素红染色及其定量,以及浓度依赖性成骨分化标志物(BMP1 和 SPP)mRNA 表达。我们的结果表明,SSZ 增强了 CADSC 的成骨分化潜力,并有可能在犬骨再生医学中表现出优异的治疗效果。
Cystine-glutamate transporter (xCT) is a plasma membrane transporter that imports cystine and indirectly contributes to the oxidative stress resistance associated with increased intracellular glutathione levels. Canine adipose-derived stem cells (CADSCs) include an xCT-positive subpopulation and show relatively low expression of osteogenic markers during in vitro osteogenic differentiation. Sulfasalazine (SSZ), a drug used to treat rheumatoid arthritis, suppresses xCT expression in cancer cells. In this study, we found that the SSZ treatment at 100 µM significantly suppressed xCT mRNA expression in CADSCs but did not significantly affect cell proliferation under the same conditions. Additionally, this treatment decreased the intracellular glutathione concentration. During in vitro osteogenic differentiation, the SSZ treatment at 50 µM and 100 µM significantly increased alizarin red staining and its quantification, as well as the concentration-dependent osteogenic differentiation markers (BMP1 and SPP) mRNA expression. Our results suggested that SSZ enhances the osteogenic differentiation potential of CADSCs and can potentially exhibit a superior therapeutic profile in canine bone regenerative medicine.