Effects of RGD-grafted phosphatidylserine-containing liposomes on the polarization of macrophages and bone tissue regeneration
Phosphatidylserine-containing liposomes (PSLs) can mimic the anti-inflammatory effects of apoptotic cells by binding to the phosphatidylserine receptors of macrophages. MGF-E8, a bridge molecule between phosphatidylserine and macrophages, can promote M2 polarization by activating macrophage integrin...
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Veröffentlicht in: | Biomaterials 2021-12, Vol.279, p.121239-121239, Article 121239 |
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description | Phosphatidylserine-containing liposomes (PSLs) can mimic the anti-inflammatory effects of apoptotic cells by binding to the phosphatidylserine receptors of macrophages. MGF-E8, a bridge molecule between phosphatidylserine and macrophages, can promote M2 polarization by activating macrophage integrin with its arginine-glycine-aspartic acid (RGD) motif. In this study, to mimic MGF-E8, PSLs presenting RGD peptide (RGD-PSLs) were prepared, and their immunomodulatory effects on macrophages and the bone tissue regeneration of rat calvarial defects were investigated. RGD peptides enhanced the phagocytosis of PSLs by macrophages, especially when the PSLs contained 3% RGD. RGD-PSLs were also more effective than PSLs for the suppression of lipopolysaccharide-induced gene expression of proinflammatory cytokines (i.e., IL-1β, IL-6, and TNF-α) as well as CD86 (M1 marker) expression. Furthermore, RGD promoted PSL-induced M2 polarization: 3%-RGD-PSLs significantly enhanced the mRNA expression of Arg-1, FIZZ1, and YM-1, as well as CD206 (M2 marker) expression. In a calvarial defect model, a significant increase in M2 with a decrease in M1 macrophages was observed with 3%-RGD-PSL treatment compared with the effects of PSLs alone. Finally, new bone formation was also accelerated by 3%-RGD-PSLs. Thus, these results suggest that the intensive immunomodulatory effect of RGD-PSLs led to the enhancement of bone tissue regeneration. |
doi_str_mv | 10.1016/j.biomaterials.2021.121239 |
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MGF-E8, a bridge molecule between phosphatidylserine and macrophages, can promote M2 polarization by activating macrophage integrin with its arginine-glycine-aspartic acid (RGD) motif. In this study, to mimic MGF-E8, PSLs presenting RGD peptide (RGD-PSLs) were prepared, and their immunomodulatory effects on macrophages and the bone tissue regeneration of rat calvarial defects were investigated. RGD peptides enhanced the phagocytosis of PSLs by macrophages, especially when the PSLs contained 3% RGD. RGD-PSLs were also more effective than PSLs for the suppression of lipopolysaccharide-induced gene expression of proinflammatory cytokines (i.e., IL-1β, IL-6, and TNF-α) as well as CD86 (M1 marker) expression. Furthermore, RGD promoted PSL-induced M2 polarization: 3%-RGD-PSLs significantly enhanced the mRNA expression of Arg-1, FIZZ1, and YM-1, as well as CD206 (M2 marker) expression. In a calvarial defect model, a significant increase in M2 with a decrease in M1 macrophages was observed with 3%-RGD-PSL treatment compared with the effects of PSLs alone. Finally, new bone formation was also accelerated by 3%-RGD-PSLs. Thus, these results suggest that the intensive immunomodulatory effect of RGD-PSLs led to the enhancement of bone tissue regeneration.</description><identifier>ISSN: 0142-9612</identifier><identifier>EISSN: 1878-5905</identifier><identifier>DOI: 10.1016/j.biomaterials.2021.121239</identifier><identifier>PMID: 34753037</identifier><language>eng</language><publisher>Netherlands: Elsevier Ltd</publisher><subject>Animals ; Bone formation ; Bone Regeneration ; Liposomes ; Macrophage ; Macrophages ; MGF-E8 ; Oligopeptides ; Phosphatidylserine ; Phosphatidylserines ; Polarization ; Rats ; RGD</subject><ispartof>Biomaterials, 2021-12, Vol.279, p.121239-121239, Article 121239</ispartof><rights>2021 Elsevier Ltd</rights><rights>Copyright © 2021 Elsevier Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c446t-45e290eaa78954be3b39ffa1baf1db961ed85cae29a1b2fb44acd1bc69159bee3</citedby><cites>FETCH-LOGICAL-c446t-45e290eaa78954be3b39ffa1baf1db961ed85cae29a1b2fb44acd1bc69159bee3</cites><orcidid>0000-0003-3553-3109 ; 0000-0002-3596-0293 ; 0000-0003-1531-9164 ; 0000-0002-0766-1106 ; 0000-0002-6916-0489</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.biomaterials.2021.121239$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34753037$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wu, Lele</creatorcontrib><creatorcontrib>Kim, Yongjoon</creatorcontrib><creatorcontrib>Seon, Gyeung Mi</creatorcontrib><creatorcontrib>Choi, Sang Hoon</creatorcontrib><creatorcontrib>Park, Hee Chul</creatorcontrib><creatorcontrib>Son, Gitae</creatorcontrib><creatorcontrib>Kim, Soung Min</creatorcontrib><creatorcontrib>Lim, Bum-Soon</creatorcontrib><creatorcontrib>Yang, Hyeong-Cheol</creatorcontrib><title>Effects of RGD-grafted phosphatidylserine-containing liposomes on the polarization of macrophages and bone tissue regeneration</title><title>Biomaterials</title><addtitle>Biomaterials</addtitle><description>Phosphatidylserine-containing liposomes (PSLs) can mimic the anti-inflammatory effects of apoptotic cells by binding to the phosphatidylserine receptors of macrophages. MGF-E8, a bridge molecule between phosphatidylserine and macrophages, can promote M2 polarization by activating macrophage integrin with its arginine-glycine-aspartic acid (RGD) motif. In this study, to mimic MGF-E8, PSLs presenting RGD peptide (RGD-PSLs) were prepared, and their immunomodulatory effects on macrophages and the bone tissue regeneration of rat calvarial defects were investigated. RGD peptides enhanced the phagocytosis of PSLs by macrophages, especially when the PSLs contained 3% RGD. RGD-PSLs were also more effective than PSLs for the suppression of lipopolysaccharide-induced gene expression of proinflammatory cytokines (i.e., IL-1β, IL-6, and TNF-α) as well as CD86 (M1 marker) expression. Furthermore, RGD promoted PSL-induced M2 polarization: 3%-RGD-PSLs significantly enhanced the mRNA expression of Arg-1, FIZZ1, and YM-1, as well as CD206 (M2 marker) expression. In a calvarial defect model, a significant increase in M2 with a decrease in M1 macrophages was observed with 3%-RGD-PSL treatment compared with the effects of PSLs alone. Finally, new bone formation was also accelerated by 3%-RGD-PSLs. Thus, these results suggest that the intensive immunomodulatory effect of RGD-PSLs led to the enhancement of bone tissue regeneration.</description><subject>Animals</subject><subject>Bone formation</subject><subject>Bone Regeneration</subject><subject>Liposomes</subject><subject>Macrophage</subject><subject>Macrophages</subject><subject>MGF-E8</subject><subject>Oligopeptides</subject><subject>Phosphatidylserine</subject><subject>Phosphatidylserines</subject><subject>Polarization</subject><subject>Rats</subject><subject>RGD</subject><issn>0142-9612</issn><issn>1878-5905</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkU9v1DAQxS1ERZfCV0AWJy5ZbMdJ1txQW9pKlSohOFv-M971KrGDnUUqBz57p2xBHHuyPPq9eXpvCHnP2Zoz3n_cr23Mk1mgRDPWtWCCr7ngolUvyIpvhk3TKda9JCvGpWhUz8UpeV3rnuGfSfGKnLZy6FrWDivy-zIEcEulOdCvVxfNtpiwgKfzLtd5Z5bo78eKRgkal9NiYoppS8c455onQFmiyw7onEdT4i_kcYCrJuNKRv0WEZM8tTkBXWKtB6AFtpCg_GHfkJOAGeDt03tGvn-5_HZ-3dzeXd2cf75tnJT90sgOhGJgzLBRnbTQ2laFYLg1gXuLCcFvOmcQwpkIVkrjPLeuV7xTFqA9Ix-Oe-eSfxygLnqK1cE4mgT5ULXoVM_4IFqJ6KcjiglqLRD0XOJkyr3mTD_2r_f6__71Y__62D-K3z35HOwE_p_0b-EIXBwBwLQ_IxRdXYTkwMeCd9A-x-f4PAB9e6IN</recordid><startdate>202112</startdate><enddate>202112</enddate><creator>Wu, Lele</creator><creator>Kim, Yongjoon</creator><creator>Seon, Gyeung Mi</creator><creator>Choi, Sang Hoon</creator><creator>Park, Hee Chul</creator><creator>Son, Gitae</creator><creator>Kim, Soung Min</creator><creator>Lim, Bum-Soon</creator><creator>Yang, Hyeong-Cheol</creator><general>Elsevier Ltd</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><orcidid>https://orcid.org/0000-0003-3553-3109</orcidid><orcidid>https://orcid.org/0000-0002-3596-0293</orcidid><orcidid>https://orcid.org/0000-0003-1531-9164</orcidid><orcidid>https://orcid.org/0000-0002-0766-1106</orcidid><orcidid>https://orcid.org/0000-0002-6916-0489</orcidid></search><sort><creationdate>202112</creationdate><title>Effects of RGD-grafted phosphatidylserine-containing liposomes on the polarization of macrophages and bone tissue regeneration</title><author>Wu, Lele ; Kim, Yongjoon ; Seon, Gyeung Mi ; Choi, Sang Hoon ; Park, Hee Chul ; Son, Gitae ; Kim, Soung Min ; Lim, Bum-Soon ; Yang, Hyeong-Cheol</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c446t-45e290eaa78954be3b39ffa1baf1db961ed85cae29a1b2fb44acd1bc69159bee3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Animals</topic><topic>Bone formation</topic><topic>Bone Regeneration</topic><topic>Liposomes</topic><topic>Macrophage</topic><topic>Macrophages</topic><topic>MGF-E8</topic><topic>Oligopeptides</topic><topic>Phosphatidylserine</topic><topic>Phosphatidylserines</topic><topic>Polarization</topic><topic>Rats</topic><topic>RGD</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wu, Lele</creatorcontrib><creatorcontrib>Kim, Yongjoon</creatorcontrib><creatorcontrib>Seon, Gyeung Mi</creatorcontrib><creatorcontrib>Choi, Sang Hoon</creatorcontrib><creatorcontrib>Park, Hee Chul</creatorcontrib><creatorcontrib>Son, Gitae</creatorcontrib><creatorcontrib>Kim, Soung Min</creatorcontrib><creatorcontrib>Lim, Bum-Soon</creatorcontrib><creatorcontrib>Yang, Hyeong-Cheol</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><jtitle>Biomaterials</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wu, Lele</au><au>Kim, Yongjoon</au><au>Seon, Gyeung Mi</au><au>Choi, Sang Hoon</au><au>Park, Hee Chul</au><au>Son, Gitae</au><au>Kim, Soung Min</au><au>Lim, Bum-Soon</au><au>Yang, Hyeong-Cheol</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Effects of RGD-grafted phosphatidylserine-containing liposomes on the polarization of macrophages and bone tissue regeneration</atitle><jtitle>Biomaterials</jtitle><addtitle>Biomaterials</addtitle><date>2021-12</date><risdate>2021</risdate><volume>279</volume><spage>121239</spage><epage>121239</epage><pages>121239-121239</pages><artnum>121239</artnum><issn>0142-9612</issn><eissn>1878-5905</eissn><abstract>Phosphatidylserine-containing liposomes (PSLs) can mimic the anti-inflammatory effects of apoptotic cells by binding to the phosphatidylserine receptors of macrophages. MGF-E8, a bridge molecule between phosphatidylserine and macrophages, can promote M2 polarization by activating macrophage integrin with its arginine-glycine-aspartic acid (RGD) motif. In this study, to mimic MGF-E8, PSLs presenting RGD peptide (RGD-PSLs) were prepared, and their immunomodulatory effects on macrophages and the bone tissue regeneration of rat calvarial defects were investigated. RGD peptides enhanced the phagocytosis of PSLs by macrophages, especially when the PSLs contained 3% RGD. RGD-PSLs were also more effective than PSLs for the suppression of lipopolysaccharide-induced gene expression of proinflammatory cytokines (i.e., IL-1β, IL-6, and TNF-α) as well as CD86 (M1 marker) expression. Furthermore, RGD promoted PSL-induced M2 polarization: 3%-RGD-PSLs significantly enhanced the mRNA expression of Arg-1, FIZZ1, and YM-1, as well as CD206 (M2 marker) expression. In a calvarial defect model, a significant increase in M2 with a decrease in M1 macrophages was observed with 3%-RGD-PSL treatment compared with the effects of PSLs alone. Finally, new bone formation was also accelerated by 3%-RGD-PSLs. Thus, these results suggest that the intensive immunomodulatory effect of RGD-PSLs led to the enhancement of bone tissue regeneration.</abstract><cop>Netherlands</cop><pub>Elsevier Ltd</pub><pmid>34753037</pmid><doi>10.1016/j.biomaterials.2021.121239</doi><tpages>1</tpages><orcidid>https://orcid.org/0000-0003-3553-3109</orcidid><orcidid>https://orcid.org/0000-0002-3596-0293</orcidid><orcidid>https://orcid.org/0000-0003-1531-9164</orcidid><orcidid>https://orcid.org/0000-0002-0766-1106</orcidid><orcidid>https://orcid.org/0000-0002-6916-0489</orcidid></addata></record> |
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subjects | Animals Bone formation Bone Regeneration Liposomes Macrophage Macrophages MGF-E8 Oligopeptides Phosphatidylserine Phosphatidylserines Polarization Rats RGD |
title | Effects of RGD-grafted phosphatidylserine-containing liposomes on the polarization of macrophages and bone tissue regeneration |
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