Nanotopographical Induction of Osteogenesis through Adhesion, Bone Morphogenic Protein Cosignaling, and Regulation of MicroRNAs

被引：130

作者：

Yang, Jingli ^{[1
]}

McNamara, Laura E. ^{[1
]}

Gadegaard, Nikolaj ^{[3
]}

Alakpa, Enateri V. ^{[1
]}

Burgess, Karl V. ^{[2
]}

Meek, R. M. Dominic ^{[4
]}

Dalby, Matthew J. ^{[1
]}

机构：

[1] Univ Glasgow, Ctr Cell Engn, Inst Mol Cell & Syst Biol, Coll Med Vet & Life Sci, Glasgow G12 8QQ, Lanark, Scotland

[2] Univ Glasgow, Scottish Poly Facil, Wolfson Wohl Canc Res Ctr, Coll Med Vet & Life Sci, Glasgow G61 1QH, Lanark, Scotland

[3] Univ Glasgow, Sch Engn, Div Biomed Engn, Glasgow G12 8LT, Lanark, Scotland

[4] So Gen Hosp, Dept Orthopaed, Glasgow G51 4TF, Lanark, Scotland

来源：

ACS NANO | 2014年 / 8卷 / 10期

基金：

英国生物技术与生命科学研究理事会; 英国工程与自然科学研究理事会;

关键词：

nanotopography; mesenchymal stem cells; metabolomics; osteogenesis; BMP and integrin signaling; MESENCHYMAL STEM-CELLS; POLYMER-DEMIXED NANOTOPOGRAPHY; OSTEOBLAST DIFFERENTIATION; PROLIFERATION; LINEAGE; SURFACES; FATE; TRANSCRIPTION; METABOLOMICS; ACTIVATION;

D O I：

10.1021/nn504767g

中图分类号：

O6 [化学];

学科分类号：

070301 [无机化学];

摘要：

It is emerging that nanotopographical information can be used to induce osteogenesis from mesenchymal stromal cells from the bone marrow, and it is hoped that this nanoscale bioactivity can be utilized to engineer next generation implants. However, the osteogenic mechanism of surfaces is currently poorly understood. In this report, we investigate mechanism and implicate bone morphogenic protein (BMP) in up-regulation of RUNX2 and show that RUNX2 and its regulatory miRNAs are BMP sensitive. Our data demonstrate that osteogenic nanotopography promotes colocalization of integrins and BMP2 receptors in order to enhance osteogenic activity and that vitronectin is important in this interface. This provides insight that topographical regulation of adhesion can have effects on signaling cascades outside of cytoskeletal signaling and that adhesions can have roles in augmenting BMP signaling.

引用

页码：9941 / 9953

页数：13

共 79 条

[1]

Smad function and intranuclear targeting share a Runx2 motif required for osteogenic lineage induction and BMP2 responsive transcription [J].