BMSC-derived exosomes carrying microRNA-122-5p promote proliferation of osteoblasts in osteonecrosis of the femoral head

Liao, Wen Ting; Yu, Ning; Xu, Haijia; Zou, Wen-Zhong; Hu, Jiyi; Liu, Xiangzhong; Yang, Yi; Li, Zhanghua

doi:10.1042/cs20181064

Cited by 123 publications

(110 citation statements)

References 58 publications

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“…Utilizing exosomes derived from different stem cells has recently become a popular area of research for treatment of ONFH [ 18 , 19 , 37 ]. Our previous research has revealed the widespread blood supply network of the femoral head [ 38 ].…”

Section: Discussionmentioning

confidence: 99%

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

Wang

et al. 2020

Stem Cell Res Ther

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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.

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Section: Discussionmentioning

confidence: 99%

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

Wang

et al. 2020

Stem Cell Res Ther

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“…Induction of ONFH caused increased expression of angiogenic responses-related genes, which were implicated in HIF-1, PI3K-Akt, and MAPK signaling pathways [39]. Mesenchymal stem cellsderived exosomal miR-122-5p protects against ONFH progression by triggering the RTK/Ras/ MAPK signaling pathway [17]. Here, our ndings indicated that miR-150-5p-overexpressed BMSC exosomes may ameliorate ONFH by promoting angiogenesis via these signaling pathways.…”

Section: Discussionmentioning

confidence: 55%

“…Next, we investigated whether exosomes overexpressed miR-150-5p could regulate angiogenesis. BMSC exosomes have been demonstrated to display therapeutic effect on various diseases including osteonecrosis [22], so we chose BMSC exosomes as miR-150-5p transporter. We rst evaluated the action of BMSC exosomes in angiogenesis.…”

Section: Bmsc Exosomes Promote Endothelial Cell Angiogenesismentioning

confidence: 99%

“…The decline of microRNA-224-3p in BMSC exosomes resulted in the upregulation of FIP200 and thereby potentiates angiogenesis and endothelial cell proliferation, invasion, and migration in traumatic ONFH [16]. Liao et al found miR-122-5p overexpressed exosomes impaired the development of ONFH by inhibiting SPRY2 expression via the RTK/Ras/MAPK signaling pathway [17]. These ndings testify that MSCs-derived exosomes can be conducive to the mend of ONFH via the transfer of speci c miRNA.…”

Section: Introductionmentioning

confidence: 99%

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MiR-150-5p-modified Bone Marrow Mesenchymal Stem Cells Derived Exosomes Ameliorate Osteonecrosis of Femoral Head by Promoting Endothelial Cell Angiogenesis

Fang¹,

He²,

Jiang³

et al. 2020

Preprint

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Background: Osteonecrosis of femoral head (ONFH) is a common ischemic disease that induces femoral head necrosis. The role of exosomes and miRNA in ONFH has been elucidated, however, whether miRNA-modified exosomes improve the therapy of ONFH is not clear.Methods: We screened ONFH-related miRNAs by RNA sequencing in plasma exosomes of ONFH patients and healthy donors. The key miRNA was overexpressed in bone marrow mesenchymal stem cells (BMSC) exosomes. The regulatory functions of miRNA-modified BMSC exosomes in vascular endothelial cells were illustrated through angiogenesis assay and scratch assay.Results: We identified 9 differently expressed miRNAs (DEmiRNAs) in plasma exosomes between ONFH and healthy groups, with 6 up-regulated and 3 down-regulated miRNAs. Function and pathway analysis revealed DEmiRNAs were primarily involved in angiogenesis, cell migration, focal adhesion. Moreover, miR-150-5p was declined in ONFH exosomes and regulated multiple angiogenesis-related pathways. The miR-150-5p-overexpressed BMSC exosomes were successfully obtained and transported miR-150-5p to endothelial cells. Moreover, the miR-150-5p-modified BMSC exosomes promoted the angiogenesis and migration of endothelial cells.Conclusion: Our results elucidate the exosomal miRNA expression profiles in ONFH, and miR-150-5p-modified BMSC exosomes protect against ONFH by promoting angiogenesis, suggesting a new molecular knowledge for the clinical application of ONFH.

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“…Utilizing exosomes derived from different stem cells has recently become a popular area of research for treatment of ONFH [19,37,38]. Our previous research has revealed the widespread blood supply network of the femoral head [39].…”

Section: Discussionmentioning

confidence: 99%

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

Wang

et al. 2020

Preprint

View full text Add to dashboard Cite

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 regulatory effect of microRNA in exosomes. Results The expression of PAI-1 was significantly increased in local microenvironment of the femoral head in 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 should be responsible for the elevated PAI-1. Moreover, we identified miR-133b-3p and tested its role as an potential inhibitor of PAI-1. Conclusions This study provided considerable evidence for BMMSC exosomal miR-mediated upregulation of the fibrinolytic regulators PAI-1 in vascular cells. The disruption of coagulation and low fibrinolysis in the femoral head will eventually lead to a disturbance in microcirculation of NONFH. We believe that our findings could be of great significance for guiding clinical trials in the future.

show abstract

BMSC-derived exosomes carrying microRNA-122-5p promote proliferation of osteoblasts in osteonecrosis of the femoral head

Cited by 123 publications

References 58 publications

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

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

MiR-150-5p-modified Bone Marrow Mesenchymal Stem Cells Derived Exosomes Ameliorate Osteonecrosis of Femoral Head by Promoting Endothelial Cell Angiogenesis

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

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