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


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Article Info

DATE

2022-07-15

AUTHORS

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

ABSTRACT

BackgroundRecent 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.MethodsHighly 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.ResultsBioinformatics 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.ConclusionsBMSC-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. More... »

PAGES

295

References to SciGraph publications

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  • Identifiers

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    http://scigraph.springernature.com/pub.10.1186/s13287-022-02975-0

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    http://dx.doi.org/10.1186/s13287-022-02975-0

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    29 schema:description BackgroundRecent 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.MethodsHighly 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.ResultsBioinformatics 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.ConclusionsBMSC-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.
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    36 BMSCs
    37 BackgroundRecent studies
    38 M1
    39 M1 macrophages
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    41 M2 macrophage polarization
    42 M2 macrophages
    43 ResultsBioinformatics analysis
    44 analysis
    45 anterior cruciate ligament reconstruction
    46 bioinformatics
    47 biomechanical tests
    48 bone
    49 bone tunnel
    50 bone volume/total volume ratio
    51 cell-derived exosomes
    52 components
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    54 cruciate ligament reconstruction
    55 early healing
    56 early inflammatory reaction
    57 effect
    58 exosomes
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    60 factor 1
    61 femur side
    62 graft
    63 group
    64 healing
    65 histological staining
    66 inflammatory reaction
    67 interface
    68 levels
    69 ligament reconstruction
    70 local stage
    71 m2
    72 macrophage polarization
    73 macrophages
    74 mechanical strength
    75 mechanism
    76 miRNA
    77 miRNAs
    78 micro-CT
    79 mimic group
    80 model
    81 number
    82 overexpressed miRNA
    83 overexpression group
    84 polarization
    85 polarization of macrophages
    86 possible mechanism
    87 rat model
    88 ratio
    89 rats
    90 reaction
    91 reconstruction
    92 regulatory factor 1
    93 repair
    94 side
    95 stage
    96 staining
    97 strength
    98 study
    99 tendon-bone healing
    100 tendon-bone interface
    101 test
    102 tibia
    103 tissue repair
    104 total volume ratio
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    108 weeks
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