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Bone mesenchymal stem cells deliver exogenous lncRNA CAHM via exosomes to regulate macrophage polarization and ameliorate intervertebral disc degeneration

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单位: [1]Huazhong Univ Sci & Technol, Union Hosp, Tongji Med Coll, Dept Ophthalmol, 1277 Jiefang Ave, Wuhan 430022, Hubei, Peoples R China [2]Huazhong Univ Sci & Technol,Tongji Hosp,Tongji Med Coll,Dept Orthoped,1095 Jiefang Ave,Wuhan 430030,Hubei,Peoples R China
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关键词: BMSCs Exosome Intervertebral disc degeneration lncRNA CAHM Macrophage polarization

摘要:
Exosomes derived from bone marrow mesenchymal stem cells (BMSC-Exos) were reported to have therapeutic potential in degenerative diseases. This study aimed to explore the effects of BMSC-Exos on inhibiting M1 macrophage polarization, reducing excessive nucleus pulposus cells (NPCs) apoptosis, and inhibiting ECM degradation during intervertebral disc degeneration (IDD). Rat IDD models were established by acupuncture. For the co-culture experiment, we used BMSC-Exo or human monocyte leukemia (THP-1) medium to incubate THP-1 or NPCs, respectively. BMSC-Exo was isolated from the BMSC medium, identified by TEM and NTA, and injected into the intervertebral discs of IDD rats. The macrophage infiltration in intervertebral disc tissue was evaluated by immunohistochemistry and immunofluorescence. ELISA was used to measure the levels of TNF-alpha, IL-6 and IL -10. The ECM degradation was analyzed by Western blot. The cell proportion and apoptosis were measured by flow cytometry. The morphological change of the intervertebral disc was analyzed by HE and safranin O fixation staining. In intervertebral disc tissues of IDD rats, we found the increased infiltration of M1 macrophages, with upregulated iNOS, TNF-alpha and IL-6 levels. Compared with BMSCs, the expression of CAHM in BMSC-Exo was significantly higher. Using co-cultured experiments, we proved that BMSC-Exo reduced apoptosis and ECM degradation of NPCs by inhibiting M1-type macrophage polarization by delivering CAHM. In addition, BMSC-Exo could improve IDD in vivo, including increased proteoglycan content, reduced macrophage infiltration and ECM degradation, and decrease expression of inflammatory factors by delivering CAHM. In conclusion, BMSC-Exo delivered exogenous CAHM via exosomes to regulate macrophage polarization and ameliorate IDD.

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出版当年[2021]版:
大类 | 3 区 医学
小类 | 4 区 肿瘤学 4 区 细胞生物学
最新[2025]版:
大类 | 3 区 生物学
小类 | 4 区 细胞生物学 4 区 肿瘤学
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出版当年[2020]版:
Q3 CELL BIOLOGY Q3 ONCOLOGY
最新[2023]版:
Q2 ONCOLOGY Q3 CELL BIOLOGY

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第一作者单位: [1]Huazhong Univ Sci & Technol, Union Hosp, Tongji Med Coll, Dept Ophthalmol, 1277 Jiefang Ave, Wuhan 430022, Hubei, Peoples R China
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