{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T15:30:47Z","timestamp":1779377447591,"version":"3.53.1"},"reference-count":48,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2015,7,1]],"date-time":"2015-07-01T00:00:00Z","timestamp":1435708800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001826","name":"Netherlands Organization for Health Research and Development","doi-asserted-by":"crossref","award":["114021001"],"award-info":[{"award-number":["114021001"]}],"id":[{"id":"10.13039\/501100001826","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Innovative Medicines Initiative Joint Undertaking, project BeTheCure","award":["115142-2"],"award-info":[{"award-number":["115142-2"]}]},{"name":"Innovative Medicines Initiative Joint Undertaking, project BeTheCure","award":["4254\/14-7"],"award-info":[{"award-number":["4254\/14-7"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecular Nutrition Food Res"],"published-print":{"date-parts":[[2015,9]]},"abstract":"<jats:sec><jats:title>Scope<\/jats:title><jats:p>This study shows the effect of bovine milk derived extracellular vesicles (BMEVs) on spontaneous polyarthritis in IL\u20101Ra\u2010deficient mice and collagen\u2010induced arthritis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and results<\/jats:title><jats:p>BMEVs were isolated from semi\u2010skimmed milk by ultracentrifugation and the particle size was around 100 nm by dynamic light scattering and electron microscopy. BMEVs expressed exosome marker CD63, immunoregulatory microRNA's (miR\u201030a, \u2010223, \u201092a), and milk\u2010specific beta\u2010casein and beta\u2010lactoglobulin mRNA. In vitro, PKH\u201067\u2010labeled BMEVs were taken up by RAW264.7, splenocytes, and intestinal cells as determined by flow cytometry and confocal microscopy. IL\u20101Ra<jats:sup>\u2212\/\u2212<\/jats:sup> mice received BMEVs by daily oral gavage starting at wk 5 till 15 after birth and collagen\u2010induced arthritis mice via their drinking water starting 1 wk before immunization till day 40. Macroscopically, BMEV treatment delayed the onset of arthritis and histology showed diminished cartilage pathology and bone marrow inflammation in both models. BMEV treatment also reduced the serum levels of MCP\u20101 and IL\u20106 and their production by splenic cells. BMEV treatment diminished the anticollagen IgG2a levels, which was accompanied by reduced splenic Th1 (Tbet) and Th17 (ROR\u03b3T) mRNA.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This is the first report that oral delivery of BMEVs ameliorates experimental arthritis and this warrants further research to determine whether this beneficial effect can be seen in rheumatoid arthritis patients.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mnfr.201500222","type":"journal-article","created":{"date-parts":[[2015,6,5]],"date-time":"2015-06-05T12:51:15Z","timestamp":1433508675000},"page":"1701-1712","source":"Crossref","is-referenced-by-count":244,"title":["Oral administration of bovine milk derived extracellular vesicles attenuates arthritis in two mouse models"],"prefix":"10.1002","volume":"59","author":[{"given":"Onno J.","family":"Arntz","sequence":"first","affiliation":[{"name":"Experimental Rheumatology Radboud University Medical Center  Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bartijn C.H.","family":"Pieters","sequence":"additional","affiliation":[{"name":"Experimental Rheumatology Radboud University Medical Center  Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina C.","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Department of Nutrition Nursing School, Universidade Federal de Minas Gerais  Belo Horizonte Minas Gerais Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathijs G.A.","family":"Broeren","sequence":"additional","affiliation":[{"name":"Experimental Rheumatology Radboud University Medical Center  Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miranda B.","family":"Bennink","sequence":"additional","affiliation":[{"name":"Experimental Rheumatology Radboud University Medical Center  Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marieke","family":"de Vries","sequence":"additional","affiliation":[{"name":"Experimental Rheumatology Radboud University Medical Center  Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter L.E.M.","family":"van Lent","sequence":"additional","affiliation":[{"name":"Experimental Rheumatology Radboud University Medical Center  Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marije I.","family":"Koenders","sequence":"additional","affiliation":[{"name":"Experimental Rheumatology Radboud University Medical Center  Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wim B.","family":"van den Berg","sequence":"additional","affiliation":[{"name":"Experimental Rheumatology Radboud University Medical Center  Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter M.","family":"van der Kraan","sequence":"additional","affiliation":[{"name":"Experimental Rheumatology Radboud University Medical Center  Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fons A.J.","family":"van de Loo","sequence":"additional","affiliation":[{"name":"Experimental Rheumatology Radboud University Medical Center  Nijmegen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,7]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11882-013-0404-6"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.3402\/fnr.v52i0.1821"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/mnfr.201400569"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/acr.22297"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.g6015"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.3109\/15476910903510806"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.2005.076901"},{"key":"e_1_2_8_9_1","first-page":"285","article-title":"Food induced (\"allergic\") arthritis: inflammatory synovitis in rabbits","volume":"17","author":"Panush R. 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