Department of Anatomy and Histology, School of Basic Medical Sciences, Tianjin Medical University, 22 Qixiangtai Road, Tianjin, 300070, China.
Key Laboratory of Hormones and Development (Ministry of Health), Tianjin Key Laboratory of Metabolic Diseases, Tianjin Medical University, Tianjin, 300070, China.
Calcif Tissue Int. 2022 Aug;111(2):171-184. doi: 10.1007/s00223-022-00976-y. Epub 2022 Apr 16.
Osteoarthritis (OA) is a whole joint disorder that is characterized by cartilage damage and abnormal remodeling of subchondral bone. Injecting adipose-derived stem cells (ASCs) into the knee joint cavity can assist in repairing osteoarthritic joints, but their ability to migrate to the damaged site is limited. Our previous studies have shown that knee loading can improve the symptoms of OA, but the effect and mechanism of knee loading on the migration of ASCs in OA remain unclear. We employed a mouse model of OA in the knee and applied knee loading (1 N at 5 Hz for 6 min/day for 2 weeks) after the intra-articular injection of ASCs. The cartilage and subchondral bone repair were assessed by histopathological analysis. Immunofluorescence assays were also used to analyze the migration of ASCs. Using cell cultures, we evaluated the migration of ASCs using the transwell migration and wound healing assays. In vivo experiments showed that knee loading promoted the migration of ASCs, increased the local SDF-1 level, and accelerated the repair of the OA-damaged sites. Mechanistically, the observed effects were blocked by the SDF-1/CXCR4 inhibitor. The in vitro results further revealed that knee loading promoted the migration of ASCs and the inhibition of SDF-1/CXCR4 significantly suppressed the beneficial loading effect. The results herein suggested that the migration of ASCs was enhanced by knee loading through the SDF-1/CXCR4 regulatory axis, and mechanical loading promoted the joint-protective effect of ASCs.
骨关节炎（OA）是一种全关节疾病，其特征是软骨损伤和软骨下骨异常重塑。将脂肪来源的干细胞（ASCs）注射到膝关节腔内有助于修复骨关节炎关节，但它们迁移到受损部位的能力有限。我们之前的研究表明，膝关节负荷可以改善 OA 的症状，但膝关节负荷对 OA 中 ASCs 迁移的影响和机制尚不清楚。我们在膝关节建立了 OA 小鼠模型，并在关节内注射 ASCs 后施加膝关节负荷（1N，5Hz，每天 6 分钟，持续 2 周）。通过组织病理学分析评估软骨和软骨下骨修复情况。还通过免疫荧光分析来分析 ASCs 的迁移。通过细胞培养，我们使用 Transwell 迁移和划痕愈合实验评估了 ASCs 的迁移。体内实验表明，膝关节负荷促进了 ASCs 的迁移，增加了局部 SDF-1 水平，并加速了 OA 损伤部位的修复。在机制上，SDF-1/CXCR4 抑制剂阻断了观察到的效果。体外结果进一步表明，膝关节负荷通过 SDF-1/CXCR4 调节轴促进了 ASCs 的迁移，而 SDF-1/CXCR4 的抑制显著抑制了有益的负荷效应。这些结果表明，膝关节负荷通过 SDF-1/CXCR4 调节轴增强了 ASCs 的迁移，机械负荷促进了 ASCs 的关节保护作用。
