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脉冲电磁场通过 Wnt/β-连环蛋白信号相关机制促进多孔钛植入物在骨缺损修复中的成骨和骨整合。

Pulsed electromagnetic fields promote osteogenesis and osseointegration of porous titanium implants in bone defect repair through a Wnt/β-catenin signaling-associated mechanism.

机构信息

Department of Biomedical Engineering, Fourth Military Medical University, Xi'an, China.

Department of Radiation Oncology, PLA 302 Hospital, Beijing, China.

出版信息

Sci Rep. 2016 Aug 24;6:32045. doi: 10.1038/srep32045.


DOI:10.1038/srep32045
PMID:27555216
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4995433/
Abstract

Treatment of osseous defects remains a formidable clinical challenge. Porous titanium alloys (pTi) have been emerging as ideal endosseous implants due to the excellent biocompatibility and structural properties, whereas inadequate osseointegration poses risks for unreliable long-term implant stability. Substantial evidence indicates that pulsed electromagnetic fields (PEMF), as a safe noninvasive method, inhibit osteopenia/osteoporosis experimentally and clinically. We herein investigated the efficiency and potential mechanisms of PEMF on osteogenesis and osseointegration of pTi in vitro and in vivo. We demonstrate that PEMF enhanced cellular attachment and proliferation, and induced well-organized cytoskeleton for in vitro osteoblasts seeded in pTi. PEMF promoted gene expressions in Runx2, OSX, COL-1 and Wnt/β-catenin signaling. PEMF-stimulated group exhibited higher Runx2, Wnt1, Lrp6 and β-catenin protein expressions. In vivo results via μCT and histomorphometry show that 6-week and 12-week PEMF promoted osteogenesis, bone ingrowth and bone formation rate of pTi in rabbit femoral bone defect. PEMF promoted femoral gene expressions of Runx2, BMP2, OCN and Wnt/β-catenin signaling. Together, we demonstrate that PEMF improve osteogenesis and osseointegration of pTi by promoting skeletal anabolic activities through a Wnt/β-catenin signaling-associated mechanism. PEMF might become a promising biophysical modality for enhancing the repair efficiency and quality of pTi in bone defect.

摘要

骨缺损的治疗仍然是一个巨大的临床挑战。多孔钛合金(pTi)由于其优异的生物相容性和结构性能,已成为理想的内植物,但骨整合不足会对植入物的长期稳定性造成不可靠的风险。大量证据表明,脉冲电磁场(PEMF)作为一种安全的非侵入性方法,在实验和临床水平上抑制骨质疏松症。本研究旨在研究 PEMF 对 pTi 体外和体内成骨和骨整合的效率和潜在机制。结果表明,PEMF 增强了细胞黏附、增殖,并诱导了 pTi 中种植的成骨细胞中组织有序的细胞骨架。PEMF 促进了 Runx2、OSX、COL-1 和 Wnt/β-catenin 信号的基因表达。PEMF 刺激组的 Runx2、Wnt1、Lrp6 和 β-catenin 蛋白表达更高。通过 μCT 和组织形态计量学的体内结果表明,6 周和 12 周 PEMF 促进了兔股骨骨缺损中 pTi 的成骨、骨内生长和骨形成率。PEMF 促进了股骨中 Runx2、BMP2、OCN 和 Wnt/β-catenin 信号的基因表达。综上所述,我们证明 PEMF 通过促进 Wnt/β-catenin 信号相关机制的骨骼合成代谢活动,改善了 pTi 的成骨和骨整合。PEMF 可能成为一种有前途的生物物理方法,可提高骨缺损中 pTi 的修复效率和质量。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f260/4995433/97609c416c5d/srep32045-f8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f260/4995433/99d76f56076a/srep32045-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f260/4995433/87bf4183deb6/srep32045-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f260/4995433/91c4964f5baa/srep32045-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f260/4995433/8bb2ee49aa35/srep32045-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f260/4995433/8c6d984693b5/srep32045-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f260/4995433/f53fd91e54a8/srep32045-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f260/4995433/71217919e6f5/srep32045-f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f260/4995433/97609c416c5d/srep32045-f8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f260/4995433/99d76f56076a/srep32045-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f260/4995433/87bf4183deb6/srep32045-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f260/4995433/91c4964f5baa/srep32045-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f260/4995433/8bb2ee49aa35/srep32045-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f260/4995433/8c6d984693b5/srep32045-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f260/4995433/f53fd91e54a8/srep32045-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f260/4995433/71217919e6f5/srep32045-f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f260/4995433/97609c416c5d/srep32045-f8.jpg

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本文引用的文献

[1]
Pulsed electromagnetic fields partially preserve bone mass, microarchitecture, and strength by promoting bone formation in hindlimb-suspended rats.

J Bone Miner Res. 2014-10

[2]
Classical and Paradoxical Effects of TNF-α on Bone Homeostasis.

Front Immunol. 2014-2-13

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Pulsed electromagnetic fields improve bone microstructure and strength in ovariectomized rats through a Wnt/Lrp5/β-catenin signaling-associated mechanism.

PLoS One. 2013-11-14

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J Craniofac Surg. 2013-11

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The effects of pulsed electromagnetic field on the functions of osteoblasts on implant surfaces with different topographies.

Acta Biomater. 2014-2

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The promotion of osseointegration of titanium surfaces by coating with silk protein sericin.

Biomaterials. 2013-1-26

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Wnt/β-catenin signaling activates bone morphogenetic protein 2 expression in osteoblasts.

Bone. 2012-9-29

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