Bone marrow mesenchymal stem cell-derived exosomes promote plasminogen activator inhibitor 1 expression in vascular cells in the local microenvironment during rabbit osteonecrosis of the femoral head
Abstract Background Nontraumatic osteonecrosis of the femoral head (NONFH) is a highly disabling orthopedic disease in young individuals. Plasminogen activator inhibitor 1 (PAI-1) has been reported to be positively associated with NONFH. We aimed to investigate the dysregulating PAI-1 in bone marrow...
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| Language: | English |
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BMC
2020-11-01
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| Series: | Stem Cell Research & Therapy |
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| Online Access: | http://link.springer.com/article/10.1186/s13287-020-01991-2 |
| _version_ | 1818339551392825344 |
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| author | Lu Li Yikai Wang Xiaobing Yu Yongming Bao Lijia An Xiaowei Wei Weiting Yu Baoyi Liu Junlei Li Jiahui Yang Yan Xia Ge Liu Fang Cao Xiuzhi Zhang Dewei Zhao |
| author_facet | Lu Li Yikai Wang Xiaobing Yu Yongming Bao Lijia An Xiaowei Wei Weiting Yu Baoyi Liu Junlei Li Jiahui Yang Yan Xia Ge Liu Fang Cao Xiuzhi Zhang Dewei Zhao |
| author_sort | Lu Li |
| collection | DOAJ |
| description | Abstract Background Nontraumatic osteonecrosis of the femoral head (NONFH) is a highly disabling orthopedic disease in young individuals. Plasminogen activator inhibitor 1 (PAI-1) has been reported to be positively associated with NONFH. We aimed to investigate the dysregulating PAI-1 in bone marrow mesenchymal stem cells (BMMSCs) and vascular cells in rabbit steroid-induced NONFH. Methods To verify the hypothesis that BMMSCs could promote thrombus formation in a paracrine manner, we collected exosomes from glucocorticoid-treated BMMSCs (GB-Exo) to determine their regulatory effects on vascular cells. microRNA sequencing was conducted to find potential regulators in GB-Exo. Utilizing gain-of-function and knockdown approaches, we testified the regulatory effect of microRNA in exosomes. Results The expression of PAI-1 was significantly increased in the local microenvironment of the femoral head in the ONFH model. GB-Exo promoted PAI-1 expression in vascular smooth muscle cells and vascular endothelial cells. We also revealed that miR-451-5p in GB-Exo plays a crucial role for the elevated PAI-1. Moreover, we identified miR-133b-3p and tested its role as a potential inhibitor of PAI-1. Conclusions This study provided considerable evidence for BMMSC exosomal miR-mediated upregulation of the fibrinolytic regulator PAI-1 in vascular cells. The disruption of coagulation and low fibrinolysis in the femoral head will eventually lead to a disturbance in the microcirculation of NONFH. We believe that our findings could be of great significance for guiding clinical trials in the future. |
| first_indexed | 2024-12-13T15:28:48Z |
| format | Article |
| id | doaj.art-093585fc3a05455489a534f5acfeff29 |
| institution | Directory Open Access Journal |
| issn | 1757-6512 |
| language | English |
| last_indexed | 2024-12-13T15:28:48Z |
| publishDate | 2020-11-01 |
| publisher | BMC |
| record_format | Article |
| series | Stem Cell Research & Therapy |
| spelling | doaj.art-093585fc3a05455489a534f5acfeff292022-12-21T23:40:16ZengBMCStem Cell Research & Therapy1757-65122020-11-0111111310.1186/s13287-020-01991-2Bone marrow mesenchymal stem cell-derived exosomes promote plasminogen activator inhibitor 1 expression in vascular cells in the local microenvironment during rabbit osteonecrosis of the femoral headLu Li0Yikai Wang1Xiaobing Yu2Yongming Bao3Lijia An4Xiaowei Wei5Weiting Yu6Baoyi Liu7Junlei Li8Jiahui Yang9Yan Xia10Ge Liu11Fang Cao12Xiuzhi Zhang13Dewei Zhao14National-Local Joint Engineering Laboratory for the Development of Orthopedic Implant Materials, Affiliated Zhongshan Hospital of Dalian UniversityNational-Local Joint Engineering Laboratory for the Development of Orthopedic Implant Materials, Affiliated Zhongshan Hospital of Dalian UniversityDepartment of Orthopedics, Affiliated Zhongshan Hospital of Dalian UniversitySchool of Bioengineering, Dalian University of TechnologySchool of Bioengineering, Dalian University of TechnologyNational-Local Joint Engineering Laboratory for the Development of Orthopedic Implant Materials, Affiliated Zhongshan Hospital of Dalian UniversityNational-Local Joint Engineering Laboratory for the Development of Orthopedic Implant Materials, Affiliated Zhongshan Hospital of Dalian UniversityNational-Local Joint Engineering Laboratory for the Development of Orthopedic Implant Materials, Affiliated Zhongshan Hospital of Dalian UniversityNational-Local Joint Engineering Laboratory for the Development of Orthopedic Implant Materials, Affiliated Zhongshan Hospital of Dalian UniversityNational-Local Joint Engineering Laboratory for the Development of Orthopedic Implant Materials, Affiliated Zhongshan Hospital of Dalian UniversityDepartment of Pathology, Affiliated Zhongshan Hospital of Dalian UniversityNational-Local Joint Engineering Laboratory for the Development of Orthopedic Implant Materials, Affiliated Zhongshan Hospital of Dalian UniversityNational-Local Joint Engineering Laboratory for the Development of Orthopedic Implant Materials, Affiliated Zhongshan Hospital of Dalian UniversityNational-Local Joint Engineering Laboratory for the Development of Orthopedic Implant Materials, Affiliated Zhongshan Hospital of Dalian UniversityNational-Local Joint Engineering Laboratory for the Development of Orthopedic Implant Materials, Affiliated Zhongshan Hospital of Dalian UniversityAbstract Background Nontraumatic osteonecrosis of the femoral head (NONFH) is a highly disabling orthopedic disease in young individuals. Plasminogen activator inhibitor 1 (PAI-1) has been reported to be positively associated with NONFH. We aimed to investigate the dysregulating PAI-1 in bone marrow mesenchymal stem cells (BMMSCs) and vascular cells in rabbit steroid-induced NONFH. Methods To verify the hypothesis that BMMSCs could promote thrombus formation in a paracrine manner, we collected exosomes from glucocorticoid-treated BMMSCs (GB-Exo) to determine their regulatory effects on vascular cells. microRNA sequencing was conducted to find potential regulators in GB-Exo. Utilizing gain-of-function and knockdown approaches, we testified the regulatory effect of microRNA in exosomes. Results The expression of PAI-1 was significantly increased in the local microenvironment of the femoral head in the ONFH model. GB-Exo promoted PAI-1 expression in vascular smooth muscle cells and vascular endothelial cells. We also revealed that miR-451-5p in GB-Exo plays a crucial role for the elevated PAI-1. Moreover, we identified miR-133b-3p and tested its role as a potential inhibitor of PAI-1. Conclusions This study provided considerable evidence for BMMSC exosomal miR-mediated upregulation of the fibrinolytic regulator PAI-1 in vascular cells. The disruption of coagulation and low fibrinolysis in the femoral head will eventually lead to a disturbance in the microcirculation of NONFH. We believe that our findings could be of great significance for guiding clinical trials in the future.http://link.springer.com/article/10.1186/s13287-020-01991-2Nontraumatic osteonecrosis of the femoral headPAI-1Bone marrow mesenchymal stem cellsExosomemiRNA |
| spellingShingle | Lu Li Yikai Wang Xiaobing Yu Yongming Bao Lijia An Xiaowei Wei Weiting Yu Baoyi Liu Junlei Li Jiahui Yang Yan Xia Ge Liu Fang Cao Xiuzhi Zhang Dewei Zhao Bone marrow mesenchymal stem cell-derived exosomes promote plasminogen activator inhibitor 1 expression in vascular cells in the local microenvironment during rabbit osteonecrosis of the femoral head Stem Cell Research & Therapy Nontraumatic osteonecrosis of the femoral head PAI-1 Bone marrow mesenchymal stem cells Exosome miRNA |
| title | Bone marrow mesenchymal stem cell-derived exosomes promote plasminogen activator inhibitor 1 expression in vascular cells in the local microenvironment during rabbit osteonecrosis of the femoral head |
| title_full | Bone marrow mesenchymal stem cell-derived exosomes promote plasminogen activator inhibitor 1 expression in vascular cells in the local microenvironment during rabbit osteonecrosis of the femoral head |
| title_fullStr | Bone marrow mesenchymal stem cell-derived exosomes promote plasminogen activator inhibitor 1 expression in vascular cells in the local microenvironment during rabbit osteonecrosis of the femoral head |
| title_full_unstemmed | Bone marrow mesenchymal stem cell-derived exosomes promote plasminogen activator inhibitor 1 expression in vascular cells in the local microenvironment during rabbit osteonecrosis of the femoral head |
| title_short | Bone marrow mesenchymal stem cell-derived exosomes promote plasminogen activator inhibitor 1 expression in vascular cells in the local microenvironment during rabbit osteonecrosis of the femoral head |
| title_sort | bone marrow mesenchymal stem cell derived exosomes promote plasminogen activator inhibitor 1 expression in vascular cells in the local microenvironment during rabbit osteonecrosis of the femoral head |
| topic | Nontraumatic osteonecrosis of the femoral head PAI-1 Bone marrow mesenchymal stem cells Exosome miRNA |
| url | http://link.springer.com/article/10.1186/s13287-020-01991-2 |
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