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M2 macrophages are obtained by stimulation of IL\u20104 with anti\u2010inflammatory and tissue repair effects. Exosomes are 30\u2013150\u2009nm lipid bilayer membrane vesicles derived from most living cells and have a variety of biological functions. Previous studies have shown that macrophage exosomes can influence the course of some autoimmune diseases, but their effect on knee osteoarthritis (KOA) has not been reported. Here, we analyze the roles of exosomes derived from M2 macrophage phenotypes in KOA rats. Exosomes were isolated from the supernatant of M2 macrophages and identified via transmission electron microscopy (TEM), Western blotting, and DLS. The results showed that M2 macrophage exosomes significantly attenuated the inflammatory response and pathological damage of articular cartilage in KOA rats. In addition, a key protein associated with KOA including Aggrecan, Col\u201010, SOX6, and Runx2 was significantly increased, while MMP\u201013 was significantly suppressed following treatment with M2 macrophage exosomes. The present study indicated that M2 macrophage exosomes exerted protective effects on KOA rats mainly mediated by the PI3K\/AKT\/mTOR signal pathway. These findings provide a novel approach for the treatment of KOA.<\/jats:p>","DOI":"10.1155\/2021\/7218067","type":"journal-article","created":{"date-parts":[[2021,12,10]],"date-time":"2021-12-10T22:05:08Z","timestamp":1639173908000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":49,"title":["Exosomes Derived from M2 Macrophages Exert a Therapeutic Effect via Inhibition of the PI3K\/AKT\/mTOR Pathway in Rats with Knee Osteoarthritic"],"prefix":"10.1155","volume":"2021","author":[{"given":"Zha Xi","family":"Da-wa","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ma","family":"Jun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liu","family":"Chao-Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Sen-Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Chuan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"De-chun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong","family":"Zu-Nan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhao","family":"Hong-tao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Shu-qing","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pei","family":"Xian-wei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3627-3337","authenticated-orcid":false,"given":"Liu","family":"Wenbo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7950-2537","authenticated-orcid":false,"given":"Li","family":"Ke-wen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,12,10]]},"reference":[{"key":"e_1_2_10_1_2","doi-asserted-by":"publisher","DOI":"10.1080\/13880209.2019.1705355"},{"key":"e_1_2_10_2_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00391-016-1062-9"},{"key":"e_1_2_10_3_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12891-020-03255-9"},{"key":"e_1_2_10_4_2","doi-asserted-by":"publisher","DOI":"10.1148\/radiol.2262012190"},{"key":"e_1_2_10_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/0006-291X(86)90881-8"},{"key":"e_1_2_10_6_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00390265"},{"key":"e_1_2_10_7_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0409781102"},{"key":"e_1_2_10_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri978"},{"key":"e_1_2_10_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2005.10.001"},{"key":"e_1_2_10_10_2","doi-asserted-by":"publisher","DOI":"10.1186\/1478-811X-11-29"},{"key":"e_1_2_10_11_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13045-017-0408-0"},{"key":"e_1_2_10_12_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-cellbio-101512-122326"},{"key":"e_1_2_10_13_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms17050712"},{"key":"e_1_2_10_14_2","doi-asserted-by":"publisher","DOI":"10.1186\/ar906"},{"key":"e_1_2_10_15_2","doi-asserted-by":"publisher","DOI":"10.1080\/15476286.2015.1017205"},{"key":"e_1_2_10_16_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-213X-8-40"},{"key":"e_1_2_10_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2008.04.003"},{"key":"e_1_2_10_18_2","first-page":"785","article-title":"Upregulation of urokinase-type plasminogen activator and inhibitor and gelatinase expression via 3 mitogen-activated protein kinases and PI3K pathways during the early development of osteoarthritis","volume":"34","author":"Hsieh Y. 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