Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul, 02841, South Korea.
Institute of Animal Molecular Biotechnology, Korea University, Seoul, 136-701, South Korea.
Biochem Biophys Res Commun. 2018 Dec 9;507(1-4):236-241. doi: 10.1016/j.bbrc.2018.11.014. Epub 2018 Nov 7.
Control of adipogenesis in mesenchymal stem cells (MSCs) offers enormous potential for management of obesity- and aging-related diseases. Celastrol, the traditional Chinese medicine extracted from Tripterygium wilfordi, exhibits anti-obesity effects in in vitro and in vivo murine models. This study describes how celastrol affects multilineage differentiation potential of human adipose-derived stem cells (hADSCs). We performed in vitro adipogenic differentiation of hADSCs and investigated how celastrol-induced lipid accumulation and expression of adipocyte differentiation markers varied with dose, duration, and donor age. In addition, we assessed the effect of celastrol on osteogenic and chondrogenic differentiation of hADSCs. During adipogenic induction of hADSCs, the inhibitory effect of celastrol on lipid accumulation and adipogenesis depended on dose, duration, time of administration, and individual donor. Inhibition was mediated by proliferator-activated receptor-γ (PPARG) and CCAAT/enhancer-binding protein alpha (CEBPA). Celastrol also suppressed differentiation of hADSCs into the osteogenic and chondrogenic lineages. Celastrol plays a regulatory role in multilineage differentiation of human MSCs. Our findings provide important insights regarding management of obesity and stem cell therapy.
脂肪细胞生成的控制为肥胖和衰老相关疾病的管理提供了巨大的潜力。雷公藤红素是从雷公藤中提取的传统中药，在体外和体内小鼠模型中均表现出抗肥胖作用。本研究描述了雷公藤红素如何影响人脂肪来源干细胞（hADSCs）的多能性分化潜能。我们对 hADSCs 进行了体外成脂分化，并研究了雷公藤红素诱导的脂质积累和脂肪细胞分化标志物的表达如何随剂量、时间和供体年龄而变化。此外，我们还评估了雷公藤红素对 hADSCs 成骨和成软骨分化的影响。在 hADSCs 的成脂诱导过程中，雷公藤红素对脂质积累和脂肪生成的抑制作用取决于剂量、时间、给药时间和个体供体。抑制作用是通过过氧化物酶体增殖物激活受体-γ（PPARG）和 CCAAT/增强子结合蛋白α（CEBPA）介导的。雷公藤红素还抑制了 hADSCs 向成骨和成软骨谱系的分化。雷公藤红素在人 MSC 的多能性分化中发挥调节作用。我们的研究结果为肥胖症的管理和干细胞治疗提供了重要的见解。
