{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T16:25:48Z","timestamp":1783700748756,"version":"3.55.0"},"reference-count":45,"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>Osteoporotic patients often suffer from bone fracture but its healing is compromised due to impaired osteogenesis potential of bone marrow-derived mesenchymal stem cells (BMSCs). Here we aimed to exploit adipose-derived stem cells from ovariectomized rats (OVX-ASCs) for bone healing. We unraveled that OVX-ASCs highly expressed miR-214 and identified 2 miR-214 targets: <jats:italic>CTNNB1<\/jats:italic> (\u03b2-catenin) and <jats:italic>TAB2<\/jats:italic>. We demonstrated that miR-214 targeting of these two genes blocked the Wnt pathway, led to preferable adipogenesis and hindered osteogenesis. As a result, OVX-ASCs implantation into OVX rats failed to heal critical-size metaphyseal bone defects. We further engineered the OVX-ASCs with a novel Cre\/loxP-based hybrid baculovirus vector that conferred prolonged expression of miR-214 sponge. Gene delivery for miR-214 sponge expression successfully downregulated miR-214 levels, activated the Wnt pathway, upregulated osteogenic factors \u03b2-catenin\/Runx2, downregulated adipogenic factors PPAR-\u03b3 and C\/EBP-\u03b1, shifted the differentiation propensity towards osteogenic lineage, enhanced the osteogenesis of co-cultured OVX-BMSCs, elevated BMP7\/osteoprotegerin secretion and hindered exosomal miR-214\/osteopontin release. Consequently, implanting the miR-214 sponge-expressing OVX-ASCs tremendously improved bone healing in OVX rats. Co-expression of miR-214 sponge and BMP2 further synergized the OVX-ASCs-mediated bone regeneration in OVX rats. This study implicates the potential of suppressing miR-214 by baculovirus-mediated gene delivery in osteoporotic ASCs for regenerative medicine.<\/jats:p>","DOI":"10.1038\/s41598-017-16547-3","type":"journal-article","created":{"date-parts":[[2017,11,20]],"date-time":"2017-11-20T10:34:20Z","timestamp":1511174060000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Baculovirus-Mediated miR-214 Knockdown Shifts Osteoporotic ASCs Differentiation and Improves Osteoporotic Bone Defects Repair"],"prefix":"10.1038","volume":"7","author":[{"given":"Kuei-Chang","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Han","family":"Chang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mu-Nung","family":"Hsu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shih-Chun","family":"Lo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wan-Hua","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Chen","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,11,24]]},"reference":[{"key":"16547_CR1","doi-asserted-by":"publisher","first-page":"363","DOI":"10.1016\/j.biomaterials.2016.01.024","volume":"83","author":"D Tang","year":"2016","unstructured":"Tang, D. et al. 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Part A"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-16547-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-16547-3","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-16547-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,23]],"date-time":"2022-12-23T14:01:19Z","timestamp":1671804079000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-16547-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,11,24]]},"references-count":45,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2017,12]]}},"alternative-id":["16547"],"URL":"https:\/\/doi.org\/10.1038\/s41598-017-16547-3","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,11,24]]},"assertion":[{"value":"22 May 2017","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 November 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":"16225"}}