Department of Biotechnology and Animal Science, National Ilan University, Ilan 260007, Taiwan.
Department of Environmental Engineering, National Ilan University, Ilan 260007, Taiwan.
Cells. 2022 Aug 12;11(16):2512. doi: 10.3390/cells11162512.
The skeletal muscle progenitors' proliferation and migration are crucial stages of myogenesis. Identifying drug candidates that contribute to myogenesis can have a positive impact on atrophying muscle. The purpose of the study is to synthesize the (AC)-β-cyclodextrin (BCD) inclusion complex (IC) and understand its in vitro pro-regenerative influence in murine skeletal C2C12 myoblasts. The IC was subjected to various nano-characterization studies. Fluorescent IC was synthesized to understand the cellular uptake of IC. Furthermore, 25 µg/mL, 12.5 µg/mL, and 6.25 µg/mL of IC were tested on murine C2C12 skeletal muscle cells for their anti-inflammatory, pro-migratory, and pro-proliferative action. The cellular internalization of IC occurred rapidly via pinocytosis. IC (252.6 ± 3.2 nm size and -37.24 ± 1.55 surface charge) exhibited anti-inflammatory action by suppressing the secretion of interleukin-6 and enhanced cell proliferation with promising cytocompatibility. A 12.5 μg/mL dose of IC promoted cell migration in 24 h, but the same dose of AC significantly reduced cell migration, suggesting modification by BCD. Molecular studies revealed that IC promoted C2C12 myoblasts migration by upregulating long non-coding RNA (lncRNA) NEAT-1, SYISL, and activating the pPKC/β-catenin pathway. Our study is the first report on the pro-proliferative and pro-migratory effects of BCD-modified extracts of AC.
成肌细胞前体的增殖和迁移是肌发生的关键阶段。确定有助于肌发生的药物候选物可以对萎缩的肌肉产生积极影响。本研究的目的是合成（AC）-β-环糊精（BCD）包合物（IC），并了解其对体外鼠骨骼肌 C2C12 成肌细胞的再生影响。对 IC 进行了各种纳米特性研究。合成荧光 IC 以了解 IC 的细胞摄取。此外，在 25 µg/mL、12.5 µg/mL 和 6.25 µg/mL 的 IC 浓度下，在鼠 C2C12 骨骼肌细胞上测试其抗炎、促迁移和促增殖作用。IC 通过胞饮作用迅速内化到细胞内。IC（252.6 ± 3.2nm 大小和-37.24 ± 1.55 表面电荷）通过抑制白细胞介素-6 的分泌表现出抗炎作用，并具有良好的细胞相容性，可增强细胞增殖。12.5µg/mL 剂量的 IC 在 24 小时内促进细胞迁移，但相同剂量的 AC 显著降低细胞迁移，这表明 BCD 对其进行了修饰。分子研究表明，IC 通过上调长链非编码 RNA（lncRNA）NEAT-1、SYISL 和激活 pPKC/β-catenin 通路促进 C2C12 成肌细胞的迁移。本研究首次报道了 BCD 修饰的 AC 提取物的促增殖和促迁移作用。
