Journal Article

BMSC-derived exosomes promote tendon-bone healing after anterior cruciate ligament reconstruction by regulating M1/M2 macrophage polarization in rats

Chen, Liaobin, Li, Zhenyu, Wang, Hui, Chen, Biao, Tong, Kai, Zhu, Jiayong, Li, Qingxian

2022

Overview

Background Recent studies have shown that bone marrow stromal cell-derived exosomes (BMSC-Exos) can be used for tissue repair. However, whether the BMSC-Exos can promote tendon-bone healing after anterior cruciate ligament reconstruction (ACLR) is still unclear. In this study, we observed in vivo and in vitro the effect of rat BMSC-Exos on tendon-bone healing after ACLR and its possible mechanism. Methods Highly expressed miRNAs in rat BMSC-Exos were selected by bioinformatics and verified in vitro . The effect of overexpressed miRNA in BMSC-Exos on M2 macrophage polarization was observed. A rat model of ACLR was established. The experimental components were divided into three groups: the control group, the BMSC-Exos group, and the BMSC-Exos with miR-23a-3p overexpression (BMSC-Exos mimic) group. Biomechanical tests, micro-CT, and histological staining were performed for analysis. Results Bioinformatics analysis showed that miR-23a-3p was highly expressed in rat BMSC-Exos and could target interferon regulatory factor 1 (IRF1, a crucial regulator in M1 macrophage polarization). In vitro, compared with the control group or the BMSC-Exos group, the BMSC-Exos mimic more significantly promoted the polarization of macrophages from M1 to M2. In vivo, at 2 weeks, the number of M2 macrophages in the early local stage of ACLR was significantly increased in the BMSC-Exos mimic group; at 4 and 8 weeks, compared with the control group or the BMSC-Exos group, the bone tunnels of the tibia and femur sides of the rats in the BMSC-Exos mimic group were significantly smaller, the interface between the graft and the bone was narrowed, the bone volume/total volume ratio (BV/TV) increased, the collagen type II alpha 1 level increased, and the mechanical strength increased. Conclusions BMSC-Exos promoted M1 macrophage to M2 macrophage polarization via miR-23a-3p, reduced the early inflammatory reaction at the tendon-bone interface, and promoted early healing after ACLR.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Anterior cruciate ligament / Arthritis / Bioinformatics / Biological response modifiers / Biomedical and Life Sciences / Biomedical Engineering and Bioengineering / Bone healing / Bone marrow / Bone marrow stromal cell / Cartilage / Cell Biology / Collagen / Collagen (type II) / Computed tomography / Exosome / Exosomes / Experiments / Femur / Inflammation / Interferon / Interferon regulatory factor / Interferon regulatory factor 1 / Joint and ligament injuries / Knee / Laboratory animals / Life Sciences / Macrophage polarization / Macrophages / Mechanical properties / Medical research / MicroRNA / miRNA / Orthopedic surgery / Osteoarthritis / Polarization / Regenerative Medicine/Tissue Engineering / Rotator cuff / Stem Cells / Tendon-bone healing / Tibia / Tunnels