{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T21:19:00Z","timestamp":1792271940239,"version":"4.4.0"},"reference-count":50,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2019,8,5]],"date-time":"2019-08-05T00:00:00Z","timestamp":1564963200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2019,8,5]],"date-time":"2019-08-05T00:00:00Z","timestamp":1564963200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81600834"],"award-info":[{"award-number":["81600834"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81772876"],"award-info":[{"award-number":["81772876"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004826","name":"Natural Science Foundation of Beijing Municipality","doi-asserted-by":"publisher","award":["L182006"],"award-info":[{"award-number":["L182006"]}],"id":[{"id":"10.13039\/501100004826","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cell Proliferation"],"published-print":{"date-parts":[[2019,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>The present study aimed to investigate whether exosomes derived from miR\u2010375\u2010overexpressing human adipose mesenchymal stem cells (hASCs) could enhance bone regeneration.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>Exosomes enriched with miR\u2010375 (Exo [miR\u2010375]) were generated from hASCs stably overexpressing miR\u2010375 after lentiviral transfection and identified with transmission electron microscopy, nanosight and western blotting. The construction efficiency of Exo (miR\u2010375) was evaluated with qRT\u2010PCR and incubated with human bone marrow mesenchymal stem cells (hBMSCs) to optimize the effective dosage. Then, the osteogenic capability of Exo (miR\u2010375) was investigated with ALP and ARS assays. Furthermore, dual\u2010luciferase reporter assay and western blotting were conducted to reveal the underlying mechanism of miR\u2010375 in osteogenic regulation. Finally, Exo (miR\u2010375) were embedded with hydrogel and applied to a rat model of calvarial defect, and \u03bc\u2010CT analysis and histological examination were conducted to evaluate the therapeutic effects of Exo (miR\u2010375) in bone regeneration.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      miR\u2010375 could be enriched in exosomes by overexpressing in the parent cells. Administration of Exo (miR\u2010375) at 50\u00a0\u03bcg\/mL improved the osteogenic differentiation of hBMSCs. With miR\u2010375 absorbed by hBMSCs,\n                      <jats:italic>insulin\u2010like growth factor binding protein 3<\/jats:italic>\n                      (\n                      <jats:italic>IGFBP3<\/jats:italic>\n                      ) was inhibited by binding to its 3\u2032UTR, and recombinant IGFBP3 protein reduced the osteogenic effects triggered by Exo (miR\u2010375). After incorporated with hydrogel, Exo (miR\u2010375) displayed a slow and controlled release, and further in vivo analysis demonstrated that Exo (miR\u2010375) enhanced the bone regenerative capacity in a rat model of calvarial defect.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Taken together, our study demonstrated that exosomes derived from miR\u2010375\u2010overexpressing hASCs promoted bone regeneration.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/cpr.12669","type":"journal-article","created":{"date-parts":[[2019,8,5]],"date-time":"2019-08-05T06:10:43Z","timestamp":1564985443000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":303,"title":["Exosomes derived from miR\u2010375\u2010overexpressing human adipose mesenchymal stem cells promote bone 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