Department of Rehabilitation Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, P. R. China.
Cell Transplant. 2021 Jan-Dec;30:963689720986142. doi: 10.1177/0963689720986142.
Mesenchymal stem cell (MSC) migration is promoted by low-intensity pulsed ultrasound (LIPUS), but its mechanism is unclear. Since autophagy is known to regulate cell migration, our study aimed to investigate if LIPUS promotes the migration of MSCs via autophagy regulation. We also aimed to investigate the effects of intra-articular injection of MSCs following LIPUS stimulation on osteoarthritis (OA) cartilage. For the study, rat bone marrow-derived MSCs were treated with an autophagy inhibitor or agonist, and then they were stimulated by LIPUS. Migration of MSCs was detected by transwell migration assays, and stromal cell-derived factor-1 (SDF-1) and C-X-C chemokine receptor type 4 (CXCR4) protein levels were quantified. For the study, a rat knee OA model was generated and treated with LIPUS after an intra-articular injection of MSCs with autophagy inhibitor added. The cartilage repair was assessed by histopathological analysis and extracellular matrix protein expression. The results suggest that LIPUS increased the expression of SDF-1 and CXCR4, and it promoted MSC migration. These effects were inhibited and enhanced by autophagy inhibitor and agonist, respectively. The results demonstrate that LIPUS significantly enhanced the cartilage repair effects of MSCs on OA, but these effects were blocked by autophagy inhibitor. Our results suggest that the migration of MSCs was enhanced by LIPUS through the activation autophagy, and LIPUS improved the protective effect of MSCs on OA cartilage via autophagy regulation.
间充质干细胞（MSC）的迁移受低强度脉冲超声（LIPUS）的促进，但具体机制尚不清楚。由于自噬已知可调节细胞迁移，因此我们的研究旨在探究 LIPUS 是否通过自噬调节来促进 MSC 的迁移。我们还旨在研究 LIPUS 刺激后关节内注射 MSC 对骨关节炎（OA）软骨的影响。在该研究中，用自噬抑制剂或激动剂处理大鼠骨髓源性 MSC，然后用 LIPUS 刺激它们。通过 Transwell 迁移实验检测 MSC 的迁移，定量基质细胞衍生因子-1（SDF-1）和 C-X-C 趋化因子受体 4（CXCR4）蛋白水平。在该研究中，建立了大鼠膝关节 OA 模型，并在关节内注射添加自噬抑制剂的 MSC 后用 LIPUS 进行治疗。通过组织病理学分析和细胞外基质蛋白表达评估软骨修复情况。结果表明，LIPUS 增加了 SDF-1 和 CXCR4 的表达，并促进了 MSC 的迁移。这些作用分别被自噬抑制剂和激动剂抑制和增强。结果表明，LIPUS 通过激活自噬显著增强了 MSC 对 OA 的软骨修复作用，但这些作用被自噬抑制剂阻断。我们的结果表明，LIPUS 通过激活自噬增强了 MSC 的迁移，并且 LIPUS 通过自噬调节改善了 MSC 对 OA 软骨的保护作用。
