{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,13]],"date-time":"2026-11-13T00:40:14Z","timestamp":1794530414678,"version":"4.9.1"},"reference-count":33,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2017,11,24]],"date-time":"2017-11-24T00:00:00Z","timestamp":1511481600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2017,11,24]],"date-time":"2017-11-24T00:00:00Z","timestamp":1511481600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Mesenchymal stem or stromal cells (MSCs) exert chondroprotective effects in preclinical models of osteoarthritis (OA). Most of their therapeutic effects are mediated via soluble mediators, which can be conveyed within extracellular vesicles (EVs). The objective of the study was to compare the respective role of exosomes (Exos) or microvesicles\/microparticles (MPs) in OA. MPs and Exos were isolated from bone marrow murine BM-MSCs through differential centrifugation. Effect of MPs or Exos was evaluated on OA-like murine chondrocytes and chondroprotection was quantified by RT-qPCR. In OA-like chondrocytes, BM-MSC-derived MPs and Exos could reinduce the expression of chondrocyte markers (type II collagen, aggrecan) while inhibiting catabolic (MMP-13, ADAMTS5) and inflammatory (iNOS) markers. Exos and MPs were also shown to protect chondrocytes from apoptosis and to inhibit\u00a0macrophage activation. <jats:italic>In vivo<\/jats:italic>, Exos or MPs were injected in the collagenase-induced OA (CIOA) model and histomorphometric analyses of joints were performed by \u00b5CT and confocal laser microscopy. BM-MSCs, MPs and Exos equally protected mice from joint damage. In conclusion, MPs and Exos exerted similar chondroprotective and anti-inflammatory function <jats:italic>in vitro<\/jats:italic> and protected mice from developing OA <jats:italic>in vivo<\/jats:italic>, suggesting that either Exos or MPs reproduced the main therapeutic effect of BM-MSCs.<\/jats:p>","DOI":"10.1038\/s41598-017-15376-8","type":"journal-article","created":{"date-parts":[[2017,11,20]],"date-time":"2017-11-20T10:10:50Z","timestamp":1511172650000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":584,"title":["Mesenchymal stem cells derived exosomes and microparticles protect cartilage and bone from degradation in osteoarthritis"],"prefix":"10.1038","volume":"7","author":[{"given":"Stella","family":"Cosenza","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maxime","family":"Ruiz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karine","family":"Toupet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Jorgensen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dani\u00e8le","family":"No\u00ebl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,11,24]]},"reference":[{"key":"15376_CR1","doi-asserted-by":"publisher","first-page":"e90633","DOI":"10.1371\/journal.pone.0090633","volume":"9","author":"C Palazzo","year":"2014","unstructured":"Palazzo, C., Ravaud, J. F., Papelard, A., Ravaud, P. & Poiraudeau, S. The burden of musculoskeletal conditions. PLoS One \n                           9, e90633 (2014).","journal-title":"PLoS One"},{"key":"15376_CR2","doi-asserted-by":"publisher","first-page":"3604","DOI":"10.1002\/art.34626","volume":"64","author":"M Ter Huurne","year":"2012","unstructured":"Ter Huurne, M. et al. Antiinflammatory and chondroprotective effects of intraarticular injection of adipose-derived stem cells in experimental osteoarthritis. Arthritis Rheum \n                           64, 3604\u20133613 (2012).","journal-title":"Arthritis Rheum"},{"key":"15376_CR3","doi-asserted-by":"publisher","first-page":"e0114962","DOI":"10.1371\/journal.pone.0114962","volume":"10","author":"K Toupet","year":"2015","unstructured":"Toupet, K. et al. Survival and biodistribution of xenogenic adipose mesenchymal stem cells is not affected by the degree of inflammation in arthritis. PLoS One \n                           10, e0114962 (2015).","journal-title":"PLoS One"},{"key":"15376_CR4","doi-asserted-by":"publisher","first-page":"3464","DOI":"10.1002\/art.11365","volume":"48","author":"JM Murphy","year":"2003","unstructured":"Murphy, J. M., Fink, D. J., Hunziker, E. B. & Barry, F. P. Stem cell therapy in a caprine model of osteoarthritis. Arthritis Rheum \n                           48, 3464\u20133474 (2003).","journal-title":"Arthritis Rheum"},{"key":"15376_CR5","doi-asserted-by":"publisher","first-page":"R22","DOI":"10.1186\/ar4156","volume":"15","author":"G Desando","year":"2013","unstructured":"Desando, G. et al. Intra-articular delivery of adipose derived stromal cells attenuates osteoarthritis progression in an experimental rabbit model. Arthritis Res Ther \n                           15, R22 (2013).","journal-title":"Arthritis Res Ther"},{"key":"15376_CR6","doi-asserted-by":"crossref","unstructured":"Pers, Y. M. et al. Adipose Mesenchymal Stromal Cell-Based Therapy for Severe Osteoarthritis of the Knee: A Phase I Dose-Escalation Trial. Stem Cells Transl Med (2016).","DOI":"10.5966\/sctm.2015-0245"},{"key":"15376_CR7","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1517\/14712598.2016.1093108","volume":"16","author":"M Ruiz","year":"2015","unstructured":"Ruiz, M., Cosenza, S., Maumus, M., Jorgensen, C. & Noel, D. Therapeutic application of mesenchymal stem cells in osteoarthritis. Expert Opin Biol Ther \n                           16, 33\u201342 (2015).","journal-title":"Expert Opin Biol Ther"},{"key":"15376_CR8","doi-asserted-by":"publisher","first-page":"834","DOI":"10.1016\/j.scr.2013.05.008","volume":"11","author":"M Maumus","year":"2013","unstructured":"Maumus, M. et al. Adipose mesenchymal stem cells protect chondrocytes from degeneration associated with osteoarthritis. Stem Cell Res \n                           11, 834\u2013844 (2013).","journal-title":"Stem Cell Res"},{"key":"15376_CR9","doi-asserted-by":"publisher","first-page":"1271","DOI":"10.1002\/art.37908","volume":"65","author":"C Manferdini","year":"2013","unstructured":"Manferdini, C. et al. Adipose-derived mesenchymal stem cells exert antiinflammatory effects on chondrocytes and synoviocytes from osteoarthritis patients through prostaglandin e2. Arthritis Rheum \n                           65, 1271\u20131281 (2013).","journal-title":"Arthritis Rheum"},{"key":"15376_CR10","doi-asserted-by":"crossref","unstructured":"Cosenza, S., Ruiz, M., Maumus, M., Jorgensen, C. & Noel, D. Pathogenic or Therapeutic Extracellular Vesicles in Rheumatic Diseases: Role of Mesenchymal Stem Cell-Derived Vesicles. Int J Mol Sci \n                           18 (2017).","DOI":"10.3390\/ijms18040889"},{"key":"15376_CR11","doi-asserted-by":"publisher","first-page":"180","DOI":"10.7150\/thno.17133","volume":"7","author":"SC Tao","year":"2017","unstructured":"Tao, S. C. et al. Exosomes derived from miR-140-5p-overexpressing human synovial mesenchymal stem cells enhance cartilage tissue regeneration and prevent osteoarthritis of the knee in a rat model. Theranostics \n                           7, 180\u2013195 (2017).","journal-title":"Theranostics"},{"key":"15376_CR12","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1186\/s13287-017-0510-9","volume":"8","author":"Y Zhu","year":"2017","unstructured":"Zhu, Y. et al. Comparison of exosomes secreted by induced pluripotent stem cell-derived mesenchymal stem cells and synovial membrane-derived mesenchymal stem cells for the treatment of osteoarthritis. Stem Cell Res Ther \n                           8, 64 (2017).","journal-title":"Stem Cell Res Ther"},{"key":"15376_CR13","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1186\/s13287-017-0632-0","volume":"8","author":"Y Wang","year":"2017","unstructured":"Wang, Y. et al. Exosomes from embryonic mesenchymal stem cells alleviate osteoarthritis through balancing synthesis and degradation of cartilage extracellular matrix. Stem Cell Res Ther \n                           8, 189 (2017).","journal-title":"Stem Cell Res Ther"},{"key":"15376_CR14","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1016\/j.jaut.2016.03.013","volume":"70","author":"AT Maria","year":"2016","unstructured":"Maria, A. T. et al. Human adipose mesenchymal stem cells as potent anti-fibrosis therapy for systemic sclerosis. J Autoimmun \n                           70, 31\u201339 (2016).","journal-title":"J Autoimmun"},{"key":"15376_CR15","doi-asserted-by":"publisher","first-page":"1253","DOI":"10.1038\/nprot.2008.95","volume":"3","author":"M Gosset","year":"2008","unstructured":"Gosset, M., Berenbaum, F., Thirion, S. & Jacques, C. Primary culture and phenotyping of murine chondrocytes. Nat Protoc \n                           3, 1253\u20131260 (2008).","journal-title":"Nat Protoc"},{"key":"15376_CR16","doi-asserted-by":"publisher","first-page":"483","DOI":"10.1002\/stem.2254","volume":"34","author":"P Luz-Crawford","year":"2016","unstructured":"Luz-Crawford, P. et al. Mesenchymal Stem Cell-Derived Interleukin 1 Receptor Antagonist Promotes Macrophage Polarization and Inhibits B Cell Differentiation. Stem Cells \n                           34, 483\u2013492 (2016).","journal-title":"Stem Cells"},{"key":"15376_CR17","doi-asserted-by":"publisher","first-page":"392","DOI":"10.3389\/fimmu.2016.00392","volume":"7","author":"M Maumus","year":"2016","unstructured":"Maumus, M. et al. Utility of a Mouse Model of Osteoarthritis to Demonstrate Cartilage Protection by IFNgamma-Primed Equine Mesenchymal Stem Cells. Front Immunol \n                           7, 392 (2016).","journal-title":"Front Immunol"},{"key":"15376_CR18","doi-asserted-by":"publisher","first-page":"e9252","DOI":"10.1371\/journal.pone.0009252","volume":"5","author":"J Maggini","year":"2010","unstructured":"Maggini, J. et al. Mouse bone marrow-derived mesenchymal stromal cells turn activated macrophages into a regulatory-like profile. PLoS One \n                           5, e9252 (2010).","journal-title":"PLoS One"},{"key":"15376_CR19","doi-asserted-by":"publisher","first-page":"380","DOI":"10.1002\/art.24229","volume":"60","author":"NR Bianco","year":"2009","unstructured":"Bianco, N. R., Kim, S. H., Ruffner, M. A. & Robbins, P. D. Therapeutic effect of exosomes from indoleamine 2,3-dioxygenase-positive dendritic cells in collagen-induced arthritis and delayed-type hypersensitivity disease models. Arthritis Rheum \n                           60, 380\u2013389 (2009).","journal-title":"Arthritis Rheum"},{"key":"15376_CR20","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1016\/j.ymthe.2005.09.015","volume":"13","author":"SH Kim","year":"2006","unstructured":"Kim, S. H. et al. Exosomes derived from genetically modified DC expressing FasL are anti-inflammatory and immunosuppressive. Mol Ther \n                           13, 289\u2013300 (2006).","journal-title":"Mol Ther"},{"key":"15376_CR21","doi-asserted-by":"publisher","first-page":"6440","DOI":"10.4049\/jimmunol.174.10.6440","volume":"174","author":"SH Kim","year":"2005","unstructured":"Kim, S. H. et al. Exosomes derived from IL-10-treated dendritic cells can suppress inflammation and collagen-induced arthritis. J Immunol \n                           174, 6440\u20136448 (2005).","journal-title":"J Immunol"},{"key":"15376_CR22","doi-asserted-by":"publisher","first-page":"315ra190","DOI":"10.1126\/scitranslmed.aac5608","volume":"7","author":"SE Headland","year":"2015","unstructured":"Headland, S. E. et al. Neutrophil-derived microvesicles enter cartilage and protect the joint in inflammatory arthritis. Sci Transl Med \n                           7, 315ra190 (2015).","journal-title":"Sci Transl Med"},{"key":"15376_CR23","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1016\/j.joca.2010.11.006","volume":"19","author":"JP Moodie","year":"2011","unstructured":"Moodie, J. P., Stok, K. S., Muller, R., Vincent, T. L. & Shefelbine, S. J. Multimodal imaging demonstrates concomitant changes in bone and cartilage after destabilisation of the medial meniscus and increased joint laxity. Osteoarthritis Cartilage \n                           19, 163\u2013170 (2011).","journal-title":"Osteoarthritis Cartilage"},{"key":"15376_CR24","doi-asserted-by":"publisher","first-page":"689","DOI":"10.1517\/14712590902936823","volume":"9","author":"QO Tang","year":"2009","unstructured":"Tang, Q. O. et al. TGF-beta3: A potential biological therapy for enhancing chondrogenesis. Expert Opin Biol Ther \n                           9, 689\u2013701 (2009).","journal-title":"Expert Opin Biol Ther"},{"key":"15376_CR25","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1177\/1534734614568373","volume":"14","author":"Y Wu","year":"2015","unstructured":"Wu, Y. et al. Mesenchymal stem cells suppress fibroblast proliferation and reduce skin fibrosis through a TGF-beta3-dependent activation. Int J Low Extrem Wounds \n                           14, 50\u201362 (2015).","journal-title":"Int J Low Extrem Wounds"},{"key":"15376_CR26","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1016\/j.matbio.2012.02.005","volume":"31","author":"A Lo Cicero","year":"2012","unstructured":"Lo Cicero, A., Majkowska, I., Nagase, H., Di Liegro, I. & Troeberg, L. Microvesicles shed by oligodendroglioma cells and rheumatoid synovial fibroblasts contain aggrecanase activity. Matrix Biol \n                           31, 229\u2013233 (2012).","journal-title":"Matrix Biol"},{"key":"15376_CR27","doi-asserted-by":"publisher","first-page":"R68","DOI":"10.1186\/ar2697","volume":"11","author":"M Pasztoi","year":"2009","unstructured":"Pasztoi, M. et al. Gene expression and activity of cartilage degrading glycosidases in human rheumatoid arthritis and osteoarthritis synovial fibroblasts. Arthritis Res Ther \n                           11, R68 (2009).","journal-title":"Arthritis Res Ther"},{"key":"15376_CR28","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1016\/j.imlet.2012.10.012","volume":"149","author":"M Pasztoi","year":"2013","unstructured":"Pasztoi, M. et al. The recently identified hexosaminidase D enzyme substantially contributes to the elevated hexosaminidase activity in rheumatoid arthritis. Immunol Lett \n                           149, 71\u201376 (2013).","journal-title":"Immunol Lett"},{"key":"15376_CR29","doi-asserted-by":"publisher","first-page":"238","DOI":"10.7150\/ijbs.10725","volume":"11","author":"L Huang","year":"2015","unstructured":"Huang, L. et al. Exosomes in mesenchymal stem cells, a new therapeutic strategy for cardiovascular diseases? Int J Biol Sci \n                           11, 238\u2013245 (2015).","journal-title":"Int J Biol Sci"},{"key":"15376_CR30","doi-asserted-by":"publisher","first-page":"914","DOI":"10.1136\/annrheumdis-2016-210426","volume":"76","author":"H Raghu","year":"2017","unstructured":"Raghu, H. et al. CCL2\/CCR2, but not CCL5\/CCR5, mediates monocyte recruitment, inflammation and cartilage destruction in osteoarthritis. Ann Rheum Dis \n                           76, 914\u2013922 (2017).","journal-title":"Ann Rheum Dis"},{"key":"15376_CR31","doi-asserted-by":"publisher","first-page":"1874","DOI":"10.3899\/jrheum.160270","volume":"43","author":"MH van den Bosch","year":"2016","unstructured":"van den Bosch, M. H. et al. Alarmin S100A9 Induces Proinflammatory and Catabolic Effects Predominantly in the M1 Macrophages of Human Osteoarthritic Synovium. J Rheumatol \n                           43, 1874\u20131884 (2016).","journal-title":"J Rheumatol"},{"key":"15376_CR32","doi-asserted-by":"publisher","first-page":"1158","DOI":"10.1016\/j.joca.2014.05.022","volume":"22","author":"RF Schelbergen","year":"2014","unstructured":"Schelbergen, R. F. et al. Treatment efficacy of adipose-derived stem cells in experimental osteoarthritis is driven by high synovial activation and reflected by S100A8\/A9 serum levels. Osteoarthritis Cartilage \n                           22, 1158\u20131166 (2014).","journal-title":"Osteoarthritis Cartilage"},{"key":"15376_CR33","doi-asserted-by":"publisher","first-page":"1208","DOI":"10.1002\/stem.2564","volume":"35","author":"Y Song","year":"2017","unstructured":"Song, Y. et al. Exosomal miR-146a Contributes to the Enhanced Therapeutic Efficacy of Interleukin-1beta-Primed Mesenchymal Stem Cells Against Sepsis. Stem Cells \n                           35, 1208\u20131221 (2017).","journal-title":"Stem Cells"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-15376-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-15376-8","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-15376-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,23]],"date-time":"2022-12-23T14:01:50Z","timestamp":1671804110000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-15376-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,11,24]]},"references-count":33,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2017,12]]}},"alternative-id":["15376"],"URL":"https:\/\/doi.org\/10.1038\/s41598-017-15376-8","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,11,24]]},"assertion":[{"value":"18 July 2017","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 October 2017","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 November 2017","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare that they have no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}],"article-number":"16214"}}