Sci Rep:杆状病毒介导的miR-214敲减或可用于骨质疏松所致的骨缺损

2017-12-01 MedSci MedSci原创

骨质疏松症患者经常会发生骨折,但由于其骨髓间充质干细胞(BMSC)的成骨能力受损,使得骨折愈合受损。在这里,研究人员旨在利用来自去卵巢大鼠(OVX-ASCs)的脂肪来源的干细胞进行骨愈合修复。结果发现,OVX-ASCs高表达miR-214,并鉴定出2个miR-214的靶点——CTNNB1(β-连环蛋白)和TAB2。研究证明miR-214靶向这两个基因可阻断Wnt通路,导致更多的脂肪形成并阻碍成骨。

骨质疏松症患者经常会发生骨折,但由于其骨髓间充质干细胞(BMSC)的成骨能力受损,使得骨折愈合受损。在这里,研究人员旨在利用来自去卵巢大鼠(OVX-ASCs)的脂肪来源的干细胞进行骨愈合修复。

结果发现,OVX-ASCs高表达miR-214,并鉴定出2个miR-214的靶点——CTNNB1(β-连环蛋白)和TAB2。研究证明miR-214靶向这两个基因可阻断Wnt通路,导致更多的脂肪形成并阻碍成骨。其结果是,OVX-ASCs植入OVX大鼠未能愈合临界尺寸的干骺端骨缺损。研究人员进一步设计了一种新的基于Cre/loxP的杂交杆状病毒载体OVX-ASCs,该载体赋予了miR-214海绵的延长表达。

miR-214海绵的表达能够成功下调miR-214的表达,激活Wnt通路,上调成骨因子β-catenin/Runx2,下调脂肪形成因子PPAR-γ和C/EBP-α,转移成向成骨细胞的分化倾向,增强共培养的OVX-BMSC的骨生成,提高BMP7/骨保护素的分泌,并阻碍外泌体miR-214/骨桥蛋白的释放。因此,植入miR-214海绵表达的OVX-ASCs极大地改善了OVX大鼠的骨愈合。在OVX大鼠中,miR-214海绵和BMP2的共表达进一步协同介导OVX-ASCs的骨再生。

综上所述,这项研究表明,骨质疏松性ASCs中通过杆状病毒介导的miR-214海绵递送可促进骨愈合,或可用于再生医学。

原始出处:

Li KC, Chang YH, Hsu MN, Lo SC, Li WH, Hu YC. Baculovirus-Mediated miR-214 Knockdown Shifts Osteoporotic ASCs Differentiation and Improves Osteoporotic Bone Defects Repair. Sci Rep. 2017 Nov 24;7(1):16225. doi: 10.1038/s41598-017-16547-3.

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    2018-10-28 smallant2002
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    2017-12-16 周周人

    学习.

    0

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    2017-12-16 周周人

    学习.

    0

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    2017-12-12 周周人

    学习.

    0

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    2017-12-03 lfcmxl
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    2017-12-03 Eleven17
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    2017-12-01 天涯183

    非常好的文章.学习了

    0