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用siMIR31HG功能化的钛表面促进骨髓间充质干细胞的成骨分化。

Titanium Surfaces Functionalized with siMIR31HG Promote Osteogenic Differentiation of Bone Marrow Mesenchymal Stem Cells.

作者信息

Huang Yiping, Zheng Yunfei, Xu Yongxiang, Li Xiaobei, Zheng Yan, Jia Lingfei, Li Weiran

机构信息

National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing Key Laboratory of Digital Stomatology, Beijing 100081, China.

出版信息

ACS Biomater Sci Eng. 2018 Aug 13;4(8):2986-2993. doi: 10.1021/acsbiomaterials.8b00432. Epub 2018 Jun 29.

Abstract

Titanium (Ti) implants are widely used in the clinic as bone substitutes and dental implants, but further improvements are needed to obtain high osteogenic ability and consequent osseointegration. Knockdown of long noncoding RNA MIR31HG promotes osteogenic differentiation and bone formation. In this study, we fabricated a Ti surface functionalized with siRNA targeting MIR31HG (siMIR31HG) and accelerated osteogenesis of bone marrow mesenchymal stem cells (BMSCs). Chitosan/siRNA complex was loaded onto the thermal alkali-treated Ti surface to fabricate the siMIR31HG-functionalized Ti surface. The surface morphology, siRNA loading and release efficiency, and transfection efficacy were investigated, and the biological effects, such as cell proliferation, cell morphology, and osteogenic activity, were determined. The results showed that the siMIR31HG-functionalized Ti implant generated an ∼50% knockdown of MIR31HG, with no apparent cytotoxicity, which consequently enhanced osteogenic differentiation of BMSCs, as indicated by the increase of ALP production, extracellular matrix mineralization, osteogenic gene expression, and ectopic bone formation in vivo. The siMIR31HG biofunctionalization can be used to obtain better osseointegration of Ti implant in the clinic.

摘要

钛(Ti)植入物作为骨替代物和牙种植体在临床上被广泛应用,但仍需要进一步改进以获得高成骨能力及随之而来的骨整合。敲低长链非编码RNA MIR31HG可促进成骨分化和骨形成。在本研究中,我们制备了一种用靶向MIR31HG的小干扰RNA(siRNA)(siMIR31HG)功能化的钛表面,并加速了骨髓间充质干细胞(BMSC)的成骨过程。将壳聚糖/siRNA复合物负载到热碱处理过的钛表面,以制备siMIR31HG功能化的钛表面。研究了其表面形态、siRNA负载和释放效率以及转染效率,并测定了细胞增殖、细胞形态和成骨活性等生物学效应。结果表明,siMIR31HG功能化的钛植入物使MIR31HG敲低约50%,且无明显细胞毒性,这进而增强了BMSC的成骨分化,体内碱性磷酸酶产量增加、细胞外基质矿化、成骨基因表达及异位骨形成均表明了这一点。siMIR31HG生物功能化可用于在临床上获得更好的钛植入物骨整合。

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