Bone mesenchymal stem cell-derived extracellular vesicles promote the repair of intervertebral disc degeneration by transferring microRNA-199a
Extracellular vesicles (EVs) secreted by bone marrow mesenchymal stem cells (BMSCs) protect intervertebral disc degeneration (IDD) by regulating nucleus pulposus cell (NPC) apoptosis. But the mechanism of BMSCs-EVs-microRNA (miR)-199a in IDD remains unclear. In this study, after the acquisition and...
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| Veröffentlicht in: | Cell cycle (Georgetown, Tex.) Tex.), 2021-02, Vol.20 (3), p.256-270 |
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| creator | Wen, Tao Wang, Hongshen Li, Yongjin Lin, Yongpeng Zhao, Shuai Liu, Jinggong Chen, Bolai |
| description | Extracellular vesicles (EVs) secreted by bone marrow mesenchymal stem cells (BMSCs) protect intervertebral disc degeneration (IDD) by regulating nucleus pulposus cell (NPC) apoptosis. But the mechanism of BMSCs-EVs-microRNA (miR)-199a in IDD remains unclear. In this study, after the acquisition and identification of BMSCs and BMSCs-EVs, IDD mouse model was established and treated with BMSCs-EVs. The pathological changes of NPCs, positive expression of MMP-2, MMP-6 and TIMP1, and the senescence and apoptosis of NPCs were evaluated. Microarray analysis was employed to analyze the differentially expressed miRs and genes after EV treatment. NPCs were treated with EVs/miR-199a/TGF-β agonist SRI-011381. The positive expression of col II and Aggrecan was assessed. The target gene and downstream pathway of miR-199a were analyzed. In vivo experiment, after BMSCs-EV treatment, MMP-2, MMP-6, TIMP1 and TUNEL-positive cells in IDD mice were decreased, and miR-199a was increased. In vitro experiments, the expression of col Ⅱ and Aggrecan, SA-β gal positive cells and apoptosis rate of NPCs were decreased after EV intervention. The protective effect of BMSCs-EVs on NPCs was impaired by reducing miR-199a carried by EVs. miR-199a could target GREM1 to inactivate the TGF-β pathway. miR-199a carried by BMSCs-EVs promotes IDD repair by targeting GREM1 and downregulating the TGF-β pathway. Our work confers a promising therapeutic strategy for IDD. |
| doi_str_mv | 10.1080/15384101.2020.1863682 |
| format | Article |
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But the mechanism of BMSCs-EVs-microRNA (miR)-199a in IDD remains unclear. In this study, after the acquisition and identification of BMSCs and BMSCs-EVs, IDD mouse model was established and treated with BMSCs-EVs. The pathological changes of NPCs, positive expression of MMP-2, MMP-6 and TIMP1, and the senescence and apoptosis of NPCs were evaluated. Microarray analysis was employed to analyze the differentially expressed miRs and genes after EV treatment. NPCs were treated with EVs/miR-199a/TGF-β agonist SRI-011381. The positive expression of col II and Aggrecan was assessed. The target gene and downstream pathway of miR-199a were analyzed. In vivo experiment, after BMSCs-EV treatment, MMP-2, MMP-6, TIMP1 and TUNEL-positive cells in IDD mice were decreased, and miR-199a was increased. In vitro experiments, the expression of col Ⅱ and Aggrecan, SA-β gal positive cells and apoptosis rate of NPCs were decreased after EV intervention. The protective effect of BMSCs-EVs on NPCs was impaired by reducing miR-199a carried by EVs. miR-199a could target GREM1 to inactivate the TGF-β pathway. miR-199a carried by BMSCs-EVs promotes IDD repair by targeting GREM1 and downregulating the TGF-β pathway. Our work confers a promising therapeutic strategy for IDD.</description><identifier>ISSN: 1538-4101</identifier><identifier>EISSN: 1551-4005</identifier><identifier>DOI: 10.1080/15384101.2020.1863682</identifier><identifier>PMID: 33499725</identifier><language>eng</language><publisher>United States: Taylor & Francis</publisher><subject>Animals ; Bone Marrow Cells - physiology ; bone mesenchymal stem cells ; Cells, Cultured ; extracellular vesicles ; Extracellular Vesicles - transplantation ; GREM1 ; Intervertebral disc degeneration ; Intervertebral Disc Degeneration - genetics ; Intervertebral Disc Degeneration - pathology ; Intervertebral Disc Degeneration - therapy ; Lumbar Vertebrae - pathology ; Male ; Mesenchymal Stem Cell Transplantation - methods ; Mesenchymal Stem Cells - physiology ; Mice ; Mice, Inbred BALB C ; MicroRNAs - genetics ; miR-199a ; nucleus pulposus cells ; Rats ; Research Paper ; TGF-β signaling pathway</subject><ispartof>Cell cycle (Georgetown, Tex.), 2021-02, Vol.20 (3), p.256-270</ispartof><rights>2021 Informa UK Limited, trading as Taylor & Francis Group 2021</rights><rights>2021 Informa UK Limited, trading as Taylor & Francis Group 2021 Informa UK Limited, trading as Taylor & Francis Group</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c468t-446d76f2c3f3b6a985d0f5a78914616e9c8913c785f02accb133f3d1e6e5090e3</citedby><cites>FETCH-LOGICAL-c468t-446d76f2c3f3b6a985d0f5a78914616e9c8913c785f02accb133f3d1e6e5090e3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7889239/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7889239/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33499725$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wen, Tao</creatorcontrib><creatorcontrib>Wang, Hongshen</creatorcontrib><creatorcontrib>Li, Yongjin</creatorcontrib><creatorcontrib>Lin, Yongpeng</creatorcontrib><creatorcontrib>Zhao, Shuai</creatorcontrib><creatorcontrib>Liu, Jinggong</creatorcontrib><creatorcontrib>Chen, Bolai</creatorcontrib><title>Bone mesenchymal stem cell-derived extracellular vesicles promote the repair of intervertebral disc degeneration by transferring microRNA-199a</title><title>Cell cycle (Georgetown, Tex.)</title><addtitle>Cell Cycle</addtitle><description>Extracellular vesicles (EVs) secreted by bone marrow mesenchymal stem cells (BMSCs) protect intervertebral disc degeneration (IDD) by regulating nucleus pulposus cell (NPC) apoptosis. But the mechanism of BMSCs-EVs-microRNA (miR)-199a in IDD remains unclear. In this study, after the acquisition and identification of BMSCs and BMSCs-EVs, IDD mouse model was established and treated with BMSCs-EVs. The pathological changes of NPCs, positive expression of MMP-2, MMP-6 and TIMP1, and the senescence and apoptosis of NPCs were evaluated. Microarray analysis was employed to analyze the differentially expressed miRs and genes after EV treatment. NPCs were treated with EVs/miR-199a/TGF-β agonist SRI-011381. The positive expression of col II and Aggrecan was assessed. The target gene and downstream pathway of miR-199a were analyzed. In vivo experiment, after BMSCs-EV treatment, MMP-2, MMP-6, TIMP1 and TUNEL-positive cells in IDD mice were decreased, and miR-199a was increased. In vitro experiments, the expression of col Ⅱ and Aggrecan, SA-β gal positive cells and apoptosis rate of NPCs were decreased after EV intervention. The protective effect of BMSCs-EVs on NPCs was impaired by reducing miR-199a carried by EVs. miR-199a could target GREM1 to inactivate the TGF-β pathway. miR-199a carried by BMSCs-EVs promotes IDD repair by targeting GREM1 and downregulating the TGF-β pathway. Our work confers a promising therapeutic strategy for IDD.</description><subject>Animals</subject><subject>Bone Marrow Cells - physiology</subject><subject>bone mesenchymal stem cells</subject><subject>Cells, Cultured</subject><subject>extracellular vesicles</subject><subject>Extracellular Vesicles - transplantation</subject><subject>GREM1</subject><subject>Intervertebral disc degeneration</subject><subject>Intervertebral Disc Degeneration - genetics</subject><subject>Intervertebral Disc Degeneration - pathology</subject><subject>Intervertebral Disc Degeneration - therapy</subject><subject>Lumbar Vertebrae - pathology</subject><subject>Male</subject><subject>Mesenchymal Stem Cell Transplantation - methods</subject><subject>Mesenchymal Stem Cells - physiology</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>MicroRNAs - genetics</subject><subject>miR-199a</subject><subject>nucleus pulposus cells</subject><subject>Rats</subject><subject>Research Paper</subject><subject>TGF-β signaling pathway</subject><issn>1538-4101</issn><issn>1551-4005</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kU2PFCEQhjtG466rP0HD0Uuv0DQ0XIy7G7-SjSZGz4ShixlMN4wFMzp_wt8snZnd6MUTleKttz6epnnO6CWjir5igqueUXbZ0a6mlORSdQ-acyYEa3tKxcMl5qpdRGfNk5y_U9qpQbPHzRnnvdZDJ86b39cpApkhQ3Sbw2wnkgvMxME0tSNg2MNI4FdBu2R2k0WyhxzcBJlsMc2pACkbIAhbG5AkT0IsgHvAAiusbmPIjoywhghoS0iRrA6k2sXsATHENZmDw_Tl01XLtLZPm0feThmend6L5tu7t19vPrS3n99_vLm6bV0vVWn7Xo6D9J3jnq-k1UqM1As7KM16ySRoVyPuBiU87axzK8arcmQgQVBNgV80r4--291qhtFBrDNNZothtngwyQbz708MG7NOezMopTuuq8HLkwGmHzvIxcx103ojGyHtsul6xeRCSFapOErrnjkj-Ps2jJqFpbljaRaW5sSy1r34e8b7qjt4VfDmKAjRJ5ztz4TTaIo9TAl9PbEL2fD_9_gD4X-yEA</recordid><startdate>20210201</startdate><enddate>20210201</enddate><creator>Wen, Tao</creator><creator>Wang, Hongshen</creator><creator>Li, Yongjin</creator><creator>Lin, Yongpeng</creator><creator>Zhao, Shuai</creator><creator>Liu, Jinggong</creator><creator>Chen, Bolai</creator><general>Taylor & Francis</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20210201</creationdate><title>Bone mesenchymal stem cell-derived extracellular vesicles promote the repair of intervertebral disc degeneration by transferring microRNA-199a</title><author>Wen, Tao ; Wang, Hongshen ; Li, Yongjin ; Lin, Yongpeng ; Zhao, Shuai ; Liu, Jinggong ; Chen, Bolai</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c468t-446d76f2c3f3b6a985d0f5a78914616e9c8913c785f02accb133f3d1e6e5090e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Animals</topic><topic>Bone Marrow Cells - physiology</topic><topic>bone mesenchymal stem cells</topic><topic>Cells, Cultured</topic><topic>extracellular vesicles</topic><topic>Extracellular Vesicles - transplantation</topic><topic>GREM1</topic><topic>Intervertebral disc degeneration</topic><topic>Intervertebral Disc Degeneration - genetics</topic><topic>Intervertebral Disc Degeneration - pathology</topic><topic>Intervertebral Disc Degeneration - therapy</topic><topic>Lumbar Vertebrae - pathology</topic><topic>Male</topic><topic>Mesenchymal Stem Cell Transplantation - methods</topic><topic>Mesenchymal Stem Cells - physiology</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>MicroRNAs - genetics</topic><topic>miR-199a</topic><topic>nucleus pulposus cells</topic><topic>Rats</topic><topic>Research Paper</topic><topic>TGF-β signaling pathway</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wen, Tao</creatorcontrib><creatorcontrib>Wang, Hongshen</creatorcontrib><creatorcontrib>Li, Yongjin</creatorcontrib><creatorcontrib>Lin, Yongpeng</creatorcontrib><creatorcontrib>Zhao, Shuai</creatorcontrib><creatorcontrib>Liu, Jinggong</creatorcontrib><creatorcontrib>Chen, Bolai</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Cell cycle (Georgetown, Tex.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wen, Tao</au><au>Wang, Hongshen</au><au>Li, Yongjin</au><au>Lin, Yongpeng</au><au>Zhao, Shuai</au><au>Liu, Jinggong</au><au>Chen, Bolai</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Bone mesenchymal stem cell-derived extracellular vesicles promote the repair of intervertebral disc degeneration by transferring microRNA-199a</atitle><jtitle>Cell cycle (Georgetown, Tex.)</jtitle><addtitle>Cell Cycle</addtitle><date>2021-02-01</date><risdate>2021</risdate><volume>20</volume><issue>3</issue><spage>256</spage><epage>270</epage><pages>256-270</pages><issn>1538-4101</issn><eissn>1551-4005</eissn><abstract>Extracellular vesicles (EVs) secreted by bone marrow mesenchymal stem cells (BMSCs) protect intervertebral disc degeneration (IDD) by regulating nucleus pulposus cell (NPC) apoptosis. But the mechanism of BMSCs-EVs-microRNA (miR)-199a in IDD remains unclear. In this study, after the acquisition and identification of BMSCs and BMSCs-EVs, IDD mouse model was established and treated with BMSCs-EVs. The pathological changes of NPCs, positive expression of MMP-2, MMP-6 and TIMP1, and the senescence and apoptosis of NPCs were evaluated. Microarray analysis was employed to analyze the differentially expressed miRs and genes after EV treatment. NPCs were treated with EVs/miR-199a/TGF-β agonist SRI-011381. The positive expression of col II and Aggrecan was assessed. The target gene and downstream pathway of miR-199a were analyzed. In vivo experiment, after BMSCs-EV treatment, MMP-2, MMP-6, TIMP1 and TUNEL-positive cells in IDD mice were decreased, and miR-199a was increased. In vitro experiments, the expression of col Ⅱ and Aggrecan, SA-β gal positive cells and apoptosis rate of NPCs were decreased after EV intervention. The protective effect of BMSCs-EVs on NPCs was impaired by reducing miR-199a carried by EVs. miR-199a could target GREM1 to inactivate the TGF-β pathway. miR-199a carried by BMSCs-EVs promotes IDD repair by targeting GREM1 and downregulating the TGF-β pathway. Our work confers a promising therapeutic strategy for IDD.</abstract><cop>United States</cop><pub>Taylor & Francis</pub><pmid>33499725</pmid><doi>10.1080/15384101.2020.1863682</doi><tpages>15</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Bone Marrow Cells - physiology bone mesenchymal stem cells Cells, Cultured extracellular vesicles Extracellular Vesicles - transplantation GREM1 Intervertebral disc degeneration Intervertebral Disc Degeneration - genetics Intervertebral Disc Degeneration - pathology Intervertebral Disc Degeneration - therapy Lumbar Vertebrae - pathology Male Mesenchymal Stem Cell Transplantation - methods Mesenchymal Stem Cells - physiology Mice Mice, Inbred BALB C MicroRNAs - genetics miR-199a nucleus pulposus cells Rats Research Paper TGF-β signaling pathway |
| title | Bone mesenchymal stem cell-derived extracellular vesicles promote the repair of intervertebral disc degeneration by transferring microRNA-199a |
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