Department of Rehabilitation Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, 210006, China.
Stem Cell Res Ther. 2019 Jan 22;10(1):41. doi: 10.1186/s13287-019-1142-z.
Low-intensity pulsed ultrasound (LIPUS) can induce mesenchymal stem cell (MSC) differentiation, although the mechanism of its potential effects on chondrogenic differentiation is unknown. Since autophagy is known to regulate the differentiation of MSCs, the aim of our study was to determine whether LIPUS induced chondrogenesis via autophagy regulation.
MSCs were isolated from the rat bone marrow, cultured in either standard or chondrogenic medium, and stimulated with 3 MHz of LIPUS given in 20% on-off cycles, with or without prior addition of an autophagy inhibitor or agonist. Chondrogenesis was evaluated on the basis of aggrecan (AGG) organization and the amount of type II collagen (COL2) and the mRNA expression of AGG, COL2, and SRY-related high mobility group-box gene 9 (SOX9) genes.
LIPUS promoted the chondrogenic differentiation of MSCs, as shown by the changes in the extracellular matrix (ECM) proteins and upregulation of chondrogenic genes, and these effects were respectively augmented and inhibited by the autophagy inhibitor and agonist.
Taken together, these results indicate that LIPUS promotes MSC chondrogenesis by inhibiting autophagy.
低强度脉冲超声(LIPUS)可诱导间充质干细胞(MSC)分化,但其对软骨分化的潜在作用机制尚不清楚。由于自噬已知可调节 MSC 的分化,因此我们的研究目的是确定 LIPUS 是否通过自噬调节诱导软骨形成。
从大鼠骨髓中分离 MSC,在标准或软骨形成培养基中培养,并接受 3MHz 的 LIPUS 刺激,以 20%的开-关周期进行,同时或不预先添加自噬抑制剂或激动剂。根据聚集蛋白(AGG)的组织和 II 型胶原(COL2)的量以及聚集蛋白、COL2 和性别决定区 Y 相关高迁移率族框基因 9(SOX9)基因的 mRNA 表达来评估软骨形成。
LIPUS 促进 MSC 的软骨分化,这表现在细胞外基质(ECM)蛋白的变化和软骨形成基因的上调,自噬抑制剂和激动剂分别增强和抑制了这些作用。
综上所述,这些结果表明,LIPUS 通过抑制自噬促进 MSC 软骨形成。